insightVol. XX No. 2 JULY 2002

Scientific Journal ofMEDICAL & VISION RESEARCH FOUNDATIONS

18, COLLEGE ROAD, CHENNAI - 600 006, INDIA

EditorialPerspective — Intraocular lens implantation in children— Geetha K Iyer, Rajesh Fogla and Srinivas K RaoMolluscum Contagiosum Mimicking Lid Tumour - A Report of a Case— Dipankar Das, Jyotirmay Biswas, S Krishnakumar and NirmalaSubramaniamDiagnostic value of polymerase chain reaction (PCR) on intraocular specimensfrom patients with viral retinitis — K Priya, J Malathi and H N MadhavanManaging the unco-operative patient under Local Anaesthesia - How We Do It— Ian SundararajMacular Changes associated with Hyper Histidinemia— Nitin S Shetty, S. Lakshmi and K. N. SulochanaLast Page - Digital Photography — Rajesh Fogla

Microphotograph of permanent section showing molluscumbodies (haematoxylin and eosin x 100)

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Advances in surgical techniques andinstrumentation, better understanding ofthe anatomy of the eye, and improvedquality of intraocular lenses, have increasedthe safety of intraocular lens (IOL)implantation in children. As a result of thisIOL's are being increasingly implanted inchildren. However IOL implantation is stillcontroversial in infants & young children,and the surgical technique & tissueresponse is different compared to adults.Our perspective article in this issue reviewsall the factors that need to be taken intoconsideration while implanting an IOL inchildren.

Accurate differentiation of herpessimplex or varicella zoster fromcytomegalovirus is essential as thetherapeutic agents differ. Rapid diagnosis

EDITORIAL

is needed for prompt initiation ofappropriate therapy and thus preservevision. In this issue Priya and colleaguesreport the diagnostic value of polymerasechain reaction on intraocular specimensfrom patients with viral retinitis.

Most of ophthalmic surgery isperformed under local anesthesia. It is notuncommon to have a difficult patient whois quite apprehensive, and claustrophobic.How do you manage these patients ? DrSundaraj explains it all in his article inthis issue.

In the era dominated by technology,photography equipments also haveundergone changes. The last page takes abrief look at digital cameras and itsapplication in ophthalmic photography.

Dr Rajesh Fogla DNB, FRCS (Edin)Editor

SIR RATAN TATA FELLOWSHIPTRAINING IN CATARACT SURGERY

(Basic & Advanced)Offered at

SANKARA NETHRALAYAWith Stipend and Accommodation

Holders of Postgraduate Diploma or Degree in Ophthalmology may apply in ownhand enclosing a detailed Bio-data with no objection certificate from the employer(if employed) to undergo training at Sankara Nethralaya.

Fellowship programme of 3 months duration is offered four times a year commencingevery 1st January, 1st April, 1st July and 1st October.

For the 1st July 2002 programme, apply before 7th June 2002.

For further details contact:The Academic Officer

Medical Research Foundation,18, College Road, Chennai 600 006

Fax: 91-44-8254180 e-mail: mrf@sankaranethralaya.org(USE FAX/E-MAIL/SPEED POST FOR CORRESPONDENCE)

3

Perspective:

Intraocular lens implantation in childrenGeetha K Iyer, Rajesh Fogla and Srinivas K Rao

Cataract surgery has improvedsignificantly over the last two decades, withadvancement in surgical techniques,instrumentation and the quality of intraocularlenses (IOL). Understanding of the pediatricocular anatomy has improved the safety ofextracapsular cataract surgery in children,and as a result of this, intraocular lenses arenow being implanted with increasingfrequency in the pediatric population.1-6

Optical rehabilitation of unilateralaphakic aniseikonia is difficult to tackle, asare the problems of optical distortion,compliance, and cosmesis associated withbilateral aphakic spectacle in children.Contact lens non-compliance, intolerance andpossible complications associated with its usemakes this modality of approach less accep-table for this age group. IOL implantationthereby offers a potentially effective means ofoptically correcting the eyes of childrenfollowing cataract surgery, and at the sametime addresses favourably the issue ofamblyopia.

IOL implantation in infants and youngchildren is still controversial with regards toIOL size, material, IOL power selection, pre-vention of opacification of the visual axis andlong term safety of the IOL in a child's eye.

This article provides an overview of allthese factors that need to be taken intoconsideration while implanting intraocularlenses in children.

1) AGEIOL implantation in children less than 2

years of age still remains controversial.Increased tissue reactivity, opacification of thevisual axis and marked axial length andrefractive changes have been cited ascontraindications to the use of IOL in the firsttwo years of life.6 The eye of an adult is 40-50% larger than a newborn child's. The mean

axial length in a newborn is 17 mm ascompared to 23.5mm in adults.7 Implantationof a regular sized IOL in the newborn asstudied in animal eyes, retards growth,indicating that pressure on the internalstructures of the eye disturbs ocular growth.6The recommendation therefore is to implantdownsized IOL's of approximately 10 mmdiameter in infants, though this requiresfurther evaluation.8 IOL implantation ininfants have been reported though the authorsconclude that it is associated with a higherrate of complications including open angleglaucoma, lens reproliferation into visual axis,pupillary membranes and corectopia, as wellas a large myopic shift occurring in the first12 to 24 months (-5.49 diopters, follow up 12months9, -6.00 diopters, follow up 41months10). A high incidence of re-operation23% to 92% was also noted when surgery wasperformed in the first year of life.9-11

Ninety percent of the crystalline lensgrowth occurs during the first two years oflife.7,12 Standard flexible IOL's of 12 mm -12.5mm diameter can be safely implanted intothe capsular bag after the age of two years.12

2) IOL POWER CALCULATIONSelection of the IOL power has been one

of the most controversial topics related topediatric IOL implantation. Selection of thedesired postoperative refraction is challengingbecause of the rapid growth of the eye ininfancy. Surgeons have chosen IOL powers tomake the eye hypermetropic13, emmetropic14,or even myopic15 in the postoperative period.

It is well known that majority of the eyegrowth takes place in the first 18 months oflife.7 Changes occur both in the axial lengthas well as the corneal curvature.(Fig 1,2) Theincrease in axial length outweighs thedecrease in corneal curvature inducing amyopic shift.7

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Fig. 2Fig. 1

of the power need for emmetropia. (table 1) Inchildren above 2 years of age, an undercorrection of 10% is sufficient and in childrenbeyond 8 years of age, one should aim foremmetropia.17,18

Undercorrection Age- 20 % 1 - 2 years age- 10 % 2 - 8 years age- emmetropia > 8 years age

Table 1Another study evaluating the long term

refractive change in pediatric pseudophakia,recommends that an appropriate IOL powercan be selected based on age, (table 2) forchildren between 2 and 15 years of age, toyield a refraction of -1.00 diopter at the ageof 20 years.19 This goal should take intoconsideration the refractive status of the felloweye in unilateral cases to keep inducedanisometropia at a reasonable level.

Age Target refraction (diopters)3 years + 5.004 years + 4.005 years + 3.006 years + 2.257 years + 1.508 years + 1.0010 years + 0.5013 years plano

Table 2

Amblyopia and form deprivation lead toalteration in the axial length towards myopia.Significant anisometropia can lead toamblyopia. Hyperopic anisometropia has thepotential to induce amblyopia more readilythan myopic anisometropia. Though it wouldtherefore seem logical to leave the eye myopicin the immediate postoperative period, it hasbeen found that myopic shift occurs fasterand is greater in myopic eyes than hyperopiceyes of the same age. Studies have shownthat the myopic shift in aphakic eyes due toan increase in the axial length is greater thanin pseudophakic eyes.16 However, the meanquantity of myopic shift is greater in thepseudophakic eyes than in the aphakic eyes.This apparent paradox is an optical pheno-menon resulting from the ever-increasingdistance of the IOL from the retina as the eyegrows. The higher the IOL power, the greaterthe myopic shift will be for pseudophakic eyescompared with aphakic eyes.

Hence it would be preferable to use amethod that mimics nature, with initialhypermetropia allowing emmetropisation tooccur with age, albeit sans accommodation.17

While deciding the IOL power, thefollowing points need to be considered -

a) AgeDahan has recommended that children

under the age of 2 years should receive 80%

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Hence, younger the child at time ofimplantation, the greater is the myopic shift.To reduce the necessity of IOL exchange, theseeyes should be undercorrected, with the residualrefractive error corrected by spectacles thatare adjusted throughout life according torefractive development. This leads to initialhypermetropia that gradually moves toemmetropia or moderate myopia in adulthood.

b) Axial length of the eyeNormal phakic eyes elongate rapidly in

the first two years of life.7 Corneal curvaturedecreases markedly during the first year oflife and changes minimally thereafter. Largemyopic shifts have been noted in infants inthe first two years following IOLimplantation.9,10 Hence IOL power can alsobe calculated on the basis of axial length inthe first two years of life.18 (Table 3)

Axial length IOL power17 mm 28 D18 mm 27 D19 mm 26 D20 mm 24 D21 mm 22 D

Table 3

c) Refractive error of fellow eyeThis has to be taken into consideration

especially in unilateral cataracts to preventanisometropia and aniseikonia. In these casesit seems appropriate to place thepseudophakic eye 1-2 diopters closer toemmetropia than the phakic eye.

d) IOL formulaeThere is no significant difference in

refractive calculation or average error amongthe SRK II, SRK-T, Holladay, and Hoffer Qformulae in children, though the Hoffer-Qformula had the lowest error.20

e) Facilitation of amblyopia treatmentTreatment of amblyopia following surgery

is crucial because emmetropisation is a visiondependent phenomenon. The advantage of

immediate postoperative emmetropiafacilitating the management of amblyopia hasto be weighed against the disadvantages oflater onset moderate to severe myopia.6 If theeye is rendered ametropic, supplementalrefractive correction, either in spectacle orcontact lens form is essential to ensureoptimal visual development.

Finally the IOL power calculation is madeon a case-by-case basis taking intoconsideration all the above-mentioned factors.

The maximum power available in IOL'sin +30 to +34D. In eyes with shorter axiallength, leaving the child with high hyperopiadefeats the very purpose of IOL implantation,especially if associated with the inability ofthe caretaker to manage spectacles or contactlenses. Piggyback IOL's have been implantedto provide a solution to this problem by theplacement of a high power IOL in the capsularbag and a low power IOL in the sulcus.11 Thelow power IOL can be removed later, thusachieving immediate postoperative emmetropiaas well as tackling the later myopic shift.11

Jacobi et al report successful implantationof zonal progressive refractive multifocal IOLin children.21 However complications such asposterior capsular opacification, opticdecentration and posterior synechiae canaffect the final visual outcome in these cases.

3) IOL BIOMATERIALS & SIZINGi) IOL Bio-Material

PMMA is the most commonly used IOLmaterial in cataract surgery, as it has thelongest safety record over a period of 50 years.The one piece all PMMA IOL exhibits bettermemory than the three piece IOL withpolypropylene haptics, resisting thepostoperative contraction of the capsular bagthereby retaining or even slightly increasingthe diameter of the capsular bag, thuslessening the tendency towards zonularstretching that occurs with the growing ciliaryring in a child.8 The flexible open loop onepiece all PMMA modified C-loop capsular IOLis recommended in eyes of children two yearsor older due to ease of insertion and the highlyflexible encircling loops.8

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Heparin surface modified (HSM) PMMAIOL's are associated with decreasedinflammatory cell deposits indicating a greaterbiocompatibility compared to the unmodifiedIOL's in pediatric cataract surgery.22

Since the popularization of phaco-emulsification, a shift towards foldable IOL'shas occurred in adults. Newer IOL's are moreflexible while retaining desirable memorycharacteristics. Foldable hydrophilic materials(hydroxyethyl-methacrylate - HEMA) are morebiocompatible than PMMA or silicone.17 Bothacrylic and silicone IOL's have beensuccessfully used in pediatric cataract surgerywith less astigmatism and minimalpostoperative inflammation.23,24

ii) IOL SizingThe crystalline lens has a mean diameter

of approximately 8.4 mm at the age of 2 yearswhich increases to 9.3 mm at the age of 16years.12 The capsular bag diameter is definedas crystalline lens diameter in mm + 1 mm.8A flexible open loop one piece all PMMA IOLwith an overall length of 12 mm to 12.5 mmis recommended for children above 2 years ofage with a mean capsular bag diameter of9.5mm.8 Ideal capsular bag implantationcreates mild stretching and ovaling of theanterior capsulotomy bag, or both, with mildstriae. Though a temporary oversizing iscreated, it accounts for the increase in axiallength and ciliary ring diameter upto puberty.With excellent capsulotomy techniques, thecapsular bag, with its high elasticity cantolerate slight oversizing.8

The adult ciliary sulcus diameter rarelyexceeds 11.5 mm diameter, hence pediatricIOL 's should not exceed 12.5 mm in overalldiameter. Larger diameter IOL's (13.5 mm) actlike loaded springs and result in compressionof ocular tissues and possibly dislocate laterdue to increased compression of the haptics.17

Moreover if placed in the ciliary sulcus thereis excessive pressure on the uveal structuresresulting in a low grade chronic uveitis aswell as IOL decentration due to unevencompression of the haptics.17,25

An IOL diameter of 10.0 mm to 11.0 mmis recommended while implanting lenses inchildren less than 2 years of age.8,17 Thesespecial pediatric lenses are manufactured byfew companies. (1: Kidlens - IOL Technologie;La Rochelle, France, 2: Palmlens - CORNEAL;Paris, France)

4) IOL POSITIONThe ideal position for an IOL is the

capsular bag because it is the most physiologicand has a long record of safety. Posteriorchamber IOL's should be used both in primaryand secondary IOL implantations.4,17 Secondaryin the bag intraocular lens implantation canbe carried out following infantile cataractsurgery without primary intraocular lensimplantation. A primary anterior and posteriorcapsulectomy of no larger than 4-5 mm isrecommended. A potential space is maintainedbetween the fused anterior and posteriorcapsular leaflets for in the bag placement ofthe IOL, which can be reopened later as asecondary procedure.26

Primary posterior continuous curvilinearcapsulorhexis (PCCC) with optic capture of theheparin coated PMMA IOL has been reportedto successfully prevent secondary opacificationof the visual axis.27 The leaflets of the anteriorand posterior capsulorhexis are apposed andsealed in front of the IOL optic except near theoptic haptic junction. This prevents proliferationof the lens epithelial cells over the anteriorhyaloid face. Another advantage of opticcapture is in enhancing IOL centration.28

Foldable acrylic IOL's also have been usedsuccessfully using similar surgical technique.23

However in another study involving childrenyounger than 5 years, it was noted that opticcapture without anterior vitrectomy did notalways ensure a clear visual axis.29,30 PCCC isnow often combined with anterior vitrectomywith or without optic capture to achieve a clearvisual axis.31,32 (Fig 3) Placement of a foldableacrylic lens has the advantage of a smallerincision combined with a larger optic diameterand minimal postoperative inflammation.23

Anterior chamber IOL's are best avoidedin children due to lack of knowledge of long

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term effects on angle structures and cornealdecompensation, in spite of the newer flexibleIOL's available, due to the long life expectancyin this group of patients.33 Iris clawintraocular lenses have been successfullyimplanted in children.34 The mean endothelialloss with these IOL's is reported to be 13.42%at the end of four years.35 It is thereforepossible that corneal decompensation mayalso occur with these IOL's in the long run.

Sulcus fixated IOL's are usuallyassociated with secondary IOLimplantation.3,36,37 Although studies havereported successful outcomes with primaryIOL implantation in the ciliary sulcus, thiscan often be associated with postoperativecomplications especially in eyes withtraumatic cataracts38, secondary to uvealtissue irritation, which may result in fibrinousuveitis and pupillary capture.25 (Fig 4)

Scleral fixated IOL's are a feasiblealternative in children with unilateral aphakiaunable to tolerate contact lenses and in theabsence of capsular support.39-41 However thisprocedure is technically more difficult to

perform in children compared to adults andthe long term risks are unknown. Besides thisit is also difficult to predict the postoperativerefraction. Complications associated with scleralfixation include suture erosion, elevatedintraocular pressure, anterior uveitis, IOLdecentration, and cystoid macular oedema.39-41

Longer follow up is required to document anyfurther complications.

5) POSTERIOR CAPSULE MANAGEMENTPosterior capsule opacification (PCO)

occurs universally in younger children aftercataract surgery and is a significant cause ofamblyopia.31 The overall percentage of PCOin patients 1 to 6 years old has been found tobe more than three times that in patients 6to 13 years old.42 PCO represents a greaterconcern in children younger than 6 years oldfor several reasons. Patients this youngusually require general anesthesia to undergolaser capsulotomy, and the amount of energyrequired to create an adequate capsularopening tends to be larger. A secondarysurgical posterior capsulotomy for fibroticmembranes places stress on the capsule andthe zonules, can cause intraocular bleedingand is associated with the anxiety and traumaof a second surgical procedure for the patientand the parents.29 Hence primary posterior

Fig 3. Slit lamp photograph (retroillumination)showing the anterior (large arrows) and theposterior (small arrows) capsulorhexis.

Fig 4. Slit lamp photograph showingopacification of the posterior capsule, notecapsulotomy – (Nd YAG) (large arrow), posteriorsynechiae (short arrow) and iris capture by theoptic of the IOL ( *) .

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capsulorhexis seems to be advisable forchildren less than six years old when cataractextraction with IOL implantation is performed.42

Although this study recommends that theposterior capsule can be left intact without theneed for anterior vitrectomy in children above theage of 6 years, another study by Vasavada et al43

recommends PCCC and anterior vitrectomyalong with optic capture of the IOL in childrenbetween 5 to 12 years of age. In his series alleyes that had vitrectomy maintained a clearvisual axis at last follow up, besidessignificantly better low contrast visual acuity.

Cystoid macular oedema (CME) has beenreported after pediatric cataract surgery withanterior vitrectomy procedure.44 However withcurrent surgical techniques, CME is not seento occur in the early period after pediatriccataract surgery.45

The use of capsular bending ring46,47,optic capture using heparin surface modifiedIOL's27 and acrylic IOL's with sharp optic edgedesign23 have also been evaluated as meansto reduce the incidence of PCO.

ConclusionIn conclusion, IOL implantation in

children beyond 2 years of age is lesscontroversial, and is the treatment of choicefor pediatric cataracts or aphakia. In the bagplacement of the IOL is essential to minimizepostoperative complications. Age and axiallength have to be considered while decidingon the IOL size and power. Foldable IOL'shave the advantage of a smaller incisioncombined with a larger optic diameter.Primary posterior capsulorhexis with anteriorvitrectomy is effective in preventingopacification of the visual axis. IOLimplantation in infants is associated withincreased complications and needs furtherevaluation.

References1. Cavallaro BE, Madigan WP, O'Hara MA,

Kramer KK, Bauman WC. Posteriorchamber intraocular lens use in children.J Pediatr Ophthalmol Strabismus. 1998;35: 254 - 263

2. Zwann J, Mullaney PB, Awad A, Al MesferS, Wheeler DT. Pediatric intraocular lensimplantation . Surgical results andcomplications in more than 300 patients.Ophthalmology 1998; 105: 112 -118

3. Sharma A, Basti S, Gupta S. Secondarycapsule supported intraocular lensimplantation in children. 1997; 23(S): 675- 680

4. Ahmadieh H, Javadi MA. Intraocular lensimplantation in children. Curr OpinOphthalmol 2001; 12: 30 - 34

5. Peterseim MW, Wilson ME. Bilateralintraocular lens implantation in thepediatric population. Ophthalmology 2000;107:1261 - 1266

6. Hutchinson AK, Wilson ME, Saunders RA.Outcomes and ocular growth rates afterintraocular lens implantation in the firsttwo years of life. J Cataract Refract Surg1998;24:846 - 852

7. Gordon RA, Donzis PB. Refractivedevelopment of the human eye. ArchOphthalmol 1985; 103: 785 - 9

8. Wilson ME, Apple DJ, Bluestein EC, WangXH. Intraocular lenses for pediatricimplantation : biomaterials, design andsizing. J Cataract Refract Surg 1994; 20:584 - 591

9. Lambert SR, Buckley EG, Plager DA,Unilateral intraocular lens implantation inthe first six months of life. J AAPOS1999;3:344-349.

10. O'Keefe M, Fenton S, Lanigan B. Visualoutcomes and complications of posteriorchamber intraocular lens implantation inthe first year of life. J Cataract RefractSurg 2001; 27 : 2006 - 2011

11. Wilson ME, Peterseim MW, Englert JA, Lall-Trail JK, Elliott LA. Pseudophakia andpolypsuedophakia in the first year of lifeJAAPOS 2001; 5: 238 - 245

12. Bluestein EC, Wilson ME, Wang XH, RustPF, Apple DJ. Dimensions of pediatriccrystalline lens: implications for intraocularlenses in children. J Pediatr OphthalmolStrabismus 1996;33: 18 - 20

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13. Dahan E, Salmenson BD. Pseudophakiain children. J cataract Refract Surg 1990;16: 75 - 82

14. Gimbel HV, Ferensowicz M, Raanan M,Deluca M. Implantation in children. JPediatr Ophthalmol Strabismus 1993; 30:69 - 79

15. Huber C. Increasing myopia in childrenwith intraocular lenses : An experiment inform deprivation myopia ? Eur J ImplantRef Surg 1993; 5: 154 - 158

16. McClatchey SK, Dahan E, Maselli E,Gimbel HV, Wilson ME, Lambert SR,Buckley EG, Freedman SF, Plager DA,Parks MM. A comparision of the rate ofrefractive growth in pediatric aphakic andpseudophakic eyes. Ophthalmology 2000;107: 118 - 122

17. Dahan E. Intraocular lens implantation inchildren. Curr Opin Ophthalmol 2000; 11:51 - 55

18. Dahan E, Drusedau MU. Choice of lensand dioptric power in pediatricpseudophakia. J Cataract Refract Surg1997; 23(S): 618 - 623

19. Plager DA, Kipfer H, Sprunger DT, SondhiN, Neely DE. Refractive change in pediatricpseudophakia: 6 year follow up. J CataractRefract Surg 2002; 28: 810 - 815

20. Andreo LK, Wilson ME, Saunders RA.Predictive value of regression andtheoretical IOL formulas in pediatricintraocular lens implantation. J PediatrOphthalmol Strabismus 1997; 34: 240 -243

21. Jacobi PC, Dietlein TS, Konen W. Multifocalintraocular lens implantation in pediatriccataract surgery. Ophthalmology 2001;108: 1375 - 1380

22. Basti S, Aasuri MK, Reddy MK, PreetamP, Reddy S, Gupta S, Naduvilath TJ.Heparin surface modified intraocularlenses in pediatric cataract surgery :prospective randomized study. J CataractRefract Surg 1999; 25: 782 - 787.

23. Argento C, Badoza D, Ugrin C. Opticcapture of the Acrysof intraocular lens inpediatric cataract surgery. J CataractRefract Surg 2001; 27: 1638 - 1642

24. Pavlovic S, Jacobi FK, Graef M, Jacobi KW.Silicone intraocular lens implantation inchildren : preliminary results. J CataractRefract Surg 2000 ; 26: 88 - 95

25. Sharma N, Pushker N, Dada T, VajpayeeRB, Dada VK. Complications of pediatriccataract surgery and intraocular lensimplantation. J Cataract Refract Surg1999; 25: 1585 - 1588

26. Wilson ME, Englert JA, Greenwald MJ. In-the-bag secondary intraocular lensimplantation in children. J AAPOS. 1999;3: 350 - 355

27. Gimbel HV. Posterior continuous curvilinearcapsulorhexis and optic capture of theintraocular lens to prevent secondaryopacification in pediatric cataract surgery.J Cataract Refract Surg 1997;23 (S): 652- 656.

28. Vasavada AR, Trivedi RH. Role of opticcapture in congenital cataract andintraocular lens surgery in children. JCataract Refract Surg 2000; 26: 824 - 831

29. Vasavada AR, Desai P. Primary PCCC withand without anterior vitrectomy incongenital cataracts. J Cataract RefractSurg 1997; 23 (S): 645 - 651

30. Hosal BM, Biglaa AW. Risk factorsassociated with secondary membraneformation after removal of pediatriccataract. . J Cataract Refract Surg 2002;28: 302 - 309

31. Koch DD, Kohen T. Retrospectivecomparision of techniques to preventsecondary cataract formation afterposterior chamber intraocular lensimplantation in infants and children. JCataract Refract Surg 1997; 23(S): 657 -663

32. Basti S, Ravishankar U, Gupta S. Resultsof a prospective evaluation of three

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in unilateral aphakic children.Ophthalmology 1999; 106: 2184 - 2189

41. Lam DS, Ng JSK, Fan DSP, Chua JKH,Leung ATS, Tham CCY. Short term resultsof scleral intraocular lens fixation inchildren. J Cataract Refract Surg 1998;24: 1474 - 1479

42. Jensen AA, Basti S, Greenwald MJ, MetsMB. When may the posterior capsule bepreserved in pediatric intraocular lenssurgery? Ophthalmology 2002; 109: 324 -327

43. Vasavada AR, Trivedi RH, Singh R.Necessity of vitrectomy when optic captureis performed in children older than 5years. J Cataract Refract Surg 2001; 27:1185 - 1193

44. Hoyt CS, Nickel B. Aphakic cystoid macularoedema; occurrence in infants and childrenafter transpupillary lensectomy andanterior vitrectomy. Arch Ophthalmol 1982;100: 742 - 749

45. Rao SK, Ravishanker K, Sitalakshmi G,Ng JS, Yu C, Lam DS. Cystoid macularoedema after pediatric intraocular lensimplantation; fluorescein angioscopyresults and literature review. J CataractRefract Surg 2001; 27: 432 - 436

46. Nishi O, Nishi K, Menapace R, Akura J:Capsular bending ring to prevent posteriorcapsule opacification: 2 year follow-up. JCataract Refract Surg 2001; 27: 1359 -1365

47. Dick HB, Schwenn O, Pfeiffer N.Implantation of the modified endocapsularbending ring in pediatric cataract surgeryusing a viscoadaptive viscoelastic agent. .J Cataract Refract Surg 1999; 25: 1432 -1436

methods of management of pediatriccataracts. Ophthalmology 1996; 103: 713- 720

33. Sawada T, Kimura W, Kimura T, Suga H,Ohte A, Yamanashi S, Ohara T. Long termfollow up of anterior chamber intraocularlens implantation. J Cataract Refract Surg1998; 24: 1515 - 1520

34. Van der pol BA, Worst JG. Iris-clawintraocular lenses in children. DocOphthalmol 1996; 92: 29 - 35

35. Menezo JL, Cisneros AL, Rodriguez-Salvador V. Endothelial study of iris clawphakic lens : four year follow up. JCataract Refract Surg 1998 ; 24: 1039 -1049

36. DeVaro JM, Buckley EG, Awner S, SeaberJ. Secondary posterior chamber intraocularlens implantation in pediatric patients. AmJ Ophthalmol 1997; 123: 24 - 30

37. Awad AH, Mullaney PB, Al-Hamad A,Wheeler D, Al-Mesfer S, Zwann J.Secondary posterior chamber intraocularlens implantation in children. J AAPOS1998; 2: 269 - 274

38. Pandey SK, Ram J, Liliana L, Brar GS,Jain AK, Gupta A, Apple DJ. Visual resultsand postoperative complications ofcapsular bag and ciliary sulcus fixation ofposterior chamber of intraocular lenses inchildren with traumatic cataracts. JCataract Refract Surg 1999; 25: 1576 -1584

39. Buckley EG. Scleral fixated (sutured)posterior chamber intraocular lensimplantation in children. J AAPOS 1999;3: 289 - 294

40. Kumar L, Arora R, Sanga L, Sota LD.Scleral fixated intraocular lens implantation

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Molluscum Contagiosum is common skininfection caused by DNA pox virus. Clinicallyit is characterized by multiple, dome shapedskin coloured nodules of varying sizes (1-3mm). Lesions are often umiblicated andyellowish cheesy material can be expressedfrom their centers. The lesions are usuallylocated on the eyelid, however, when the lesionoccurs at the lid margin and is single it maycause a diagnostic dilemma.

We report a case of molluscumcontagiosum in a HIV negative patient whereinit mimicked a lid tumor. Subsequently, frozensection as well as histopathologicalexamination revealed it to be molluscumcontagiosum.

Case reportA 51 year old lady visited our institute

in July 1993 with history of seeing flashes oflight of 1 month duration and occasional painin both eyes. She had history of myopia sincechildhood. On examination, her best correctedvisual acuity was 6/12; N6 in the right eyeand 6/9; N6 in the left eye. Slit lampexamination revealed no abnormality. Fundus

Molluscum Contagiosum Mimicking LidTumour - A Report of a CaseDipankar Das, Jyotirmay Biswas, S Krishnakumar and Nirmala Subramaniam

examination revealed a horseshoe tear in theright eye and a pigmented lattice degenerationin the left eye. Prophylactic laser photo-coagulation around the horseshoe tear andlattice degeneration was done in both eyes.

Patient was subsequently seen 8 yearslater with swelling on the left upper eyelid of6 months duration and increase in size since2 months. On slit lamp examination, a small,non tender, elevated, yellowish, umblicatedswelling with loss of cilia that did not bleedon touch was seen. Ipsilateral preauricularlymphnode was palpable. Clinically adifferential diagnosis of keratoacanthoma,sebaceous gland carcinoma and nodular basalcell carcinoma was entertained.

She was advised for excision biopsy ofthe lesion under frozen section control witheyelid reconstruction. Systemic examinationrevealed no evidence of malignancy. Patientunderwent excision biopsy of the lid mass.Frozen section examination of the lesionrevealed features consistent with molluscumcontagiosum and subsequently the permanent

Fig. 1 Clinical photograph showing anumbilicated lesion in the left upper eyelid.

Fig. 2 Microphotograph showing frozen sectionstudy of excised biopsy showing acanthoticepithelium and multiple eosinophilic molluscumbodies (haematoxylin and eosin x 100)

12

section confirmed the findings. On lightmicroscopy, this lesion showed acanthoticepithelium. Within the epithelium,innumerable round and oval eosinophilicintracytoplasmic inclusion bodies consistentwith molluscum contagiosum was seen.Patient was assured and advised no treatment.

Discussion:Tumors in the lid could present as a

solitary nodule, with umblication inkeretoacanthoma, basal cell carcinoma,sebaceous gland carcinoma, squamous cellcarcinoma. Clinically occasionally it becomesdifficult to make an unequivocal diagnosis ofany of the above conditions. Molluscumcontagiosum is usually umbilicated mostlysituated on the eyelid surface and multiple innumber. Molluscum contagiosum in the eyelidhas been reported in patients with AIDS4.These are larger than non-HIV patients andoften confluent. However, such a lesion in nonHIV patient is rare. Our patient had singlelarge eyelid lesions.

Keratoacanthoma is a specialized variantof pseudocarcinomatous hyperplasia thatoccurs mainly in exposed areas of the skinand usually develops in a period of weeks ora few months. Clinically, a typicalkeratoacanthoma appears as a dome shapednodule with central keratin filled crater andelevated, rolled margins. Microscopicexamination of a typical eyelidkeratoacanthoma discloses a cup shaped

nodular elevation and thickening of epidermiscontaining well-differentiated squamousepithelium surrounding a central mass ofkeratin. Frequently, the base of the lesion israther uniform and well demarcated from theadjacent dermis by moderate inflammatoryreaction. Collections of neutrophils formingmicroabscesses are usually present withinsome of the islands of squamous epithelium.1

The nodulo-ulcerative type of basal cellcarcinoma appears clinically as a raised,pearly nodule, often exhibiting smalltelangiectatic vessels on this surface. As thenodule slowly increases in size, it mayundergo central ulceration; eventually thelesion may appear as a slowly enlarging ulcersurrounded by prominent rolled border (rodentulcer)2

Squamous cell carcinoma typically affectselderly, fair skinned individuals, mostcommonly it involves the margin the lowerlid, but it may be located elsewhere in theeyelid. Clinically, the lesion usually manifestsas an elevated, indurated plaque or nodulethat tends to ulcerate and exhibits irregularborders. In well differentiated tumors, themasses of keratin may give the lesion agrayish white, granular appearance.

Sebaceous gland carcinoma consists of1 to 3% of all lid tumors.3 The disease affectselderly patients. Rarely it may occur beforethe age of 40. Sebaceous gland carcinoma canexhibit a broad spectrum of clinical features.Mostly commonly, it is presents as a small,diffuse plaque like thickening. It may alsopresent as as a localized thickening of thelids associated with loss of lashes. The latterfinding is caused by neoplastic involvementof the follicles of the lashes.

Though molluscum contagiosum can beseen as multiple, large and confluent lesions,it can also be seen a single large andumblicated lesion mimicking a neoplasm.Ophthalmologists and the other eye carepersonnel therefore should be aware of variouspresentations of molluscum contagiosum. Wefeel in such diagnositic dilemma, excisionbiopsy under frozen section control is advised.

Fig. 3 Microphotograph of permanent sectionshowing molluscum bodies (haematoxylin andeosin x 100)

13

Electrocautery, chemical cautery, cryotherapyand surgical excision are the varioustreatment modalities described for molluscumcontagiosum lesions.

References

1. Stewart WB, Nicholson DH, Hamilton G etal: Eyelid tumors and renaltransplantation. Archives of Ophthalmology1980; 98: 1771-1772.

2. Zackheim HS, Howell AB and Loud AV:Nevoid basal cell carcinoma syndrome.

Some histologic observations on thecutaneous lesions. Arch Dermetol 1966;93: 317-323.

3. Rao NA, Hidyat AA, Mclean IW,Zimmerman LE: Sebaceous glandcarcinoma of ocular adnexa: Aclinicopathologic study of 104 cases withfive year follow up data. Hum Pathol 1982;13: 113-122

4. Charles NC, Friedberg DN: Epibulbarmolluscum contagiosum in AIDS.Ophthalmology 1992; 99: 1123-36.

PLEASE LOOK US UP ON THE WEB athttp://www.sankaranethralaya.org

Please forward your correct address with your E-mail address if any,to enable us to update our address data base.

14

CME PROGRAMMES FOR THE SILVER JUBILEE YEAR 2002 – 2003

This Academic Year being the “Silver Jubilee Year” of Sankara Nethralayaattracts special significance and importance. Apart from the continuous effortsdirected towards improvement of Patient’s Care and Patient’s Education onprevention and cure, the foundation has also lined up various CME Programmesfor Ophthalmologists and Optometrists for updating their skill and knowledge.

Sl.No. Topics Date

1. Uveitis & Systemic Diseases 29.06.2002

2. Revision Course in Ophthalmology for FRCS 26.06.2002 to 02.07.2002Exam going students

3. Contact Lens 31.08.2002

4. Update in Neuro-ophthalmology 26.10.2002 to 27.10.2002

5. Low Vision Aids 30.11.2002

6. Small Incision Cataract Surgery 14.12.2002 & 15.12.2002

7. Cornea 07.03.2003 to 09.03.2003

8. Revision course in ophthalmology for 25.06.2003 to 01.07.2003FRCS / MRCS exam going students

9. Paediatric Ophthalmology 05.07.2003 & 06.07.2003

10. Vitreo-retina 07.09.2003 & 08.09.2003

11. Glaucoma 06.12.2003 & 07.12.2003

The programmes are aimed to provide continuing medical education to the practisingOphthalmologists, Residents in Ophthalmology and to the Optometrists.

FOR MORE DETAILS, PLEASE CONTACT

Mr. N. SivakumarThe Academic Officer

SANKARA NETHRALAYA18, College Road

CHENNAI – 600 006Fax: 91-44-8254180

Email: academic@sankaranethralaya.org

15

Multicentric trial of Intravitreal steroid implant innon-infectious uveitis affecting the posterior segment of the eyeYou would be glad to know that Sankara Nethralaya is doing a project“A Multicenter, Randomized, Double masked, Controlled Study to evaluate thesafety and efficacy of an Intravitreal Fluocinolone Acetonide (0.5 or 2 mg) Implantin patients with non infectious uveitis affecting the posterior segment of eye”.

This 3 year global clinical trial is to evaluate the efficacy and safety of a newIntravitreal device in the management of posterior uveitis. This trial is beingconducted concurrently in the United States, Australia, Europe, Canada andSingapore. The information from this trial will be part of an FDA submission forapproval. In India besides our institute two other teaching institutions are involvedin the trial.

I request you to consider referring patients who meet the following criteria:1. Males and non-pregnant females over 6 years of age.2. Uveitis of one or more years duration.3. Patients who have received systemic therapy (steroids or immunosuppresants)

or periocular steroids as part of their treatment for the uveitis.4. Atleast 2 separate recurrences within the last six months requiring either

systemic corticosteroids therapy or subtenon’s injection of corticosteroids.

From a diagnostic standpoint this would mean patients with the followingdiagnosis:

Intermediate uveitis (parsplanitis)Sympathetic ophthalmiaVogt Koyanagi Harada DiseaseBehcet’s diseaseIdiopathic posterior uveitis

We shall undertake a complete assessment of the patient at no expense to thepatient and if found suitable, will receive the implant. All patients on the studyare administered an informed consent prior to the study.

If your patient is found suitable for the study, I shall be sending you periodicupdates of your patient. However, if the patient does not meet the inclusioncriteria, I shall also inform you and the patient would be referred back to youfor further treatment.

I would also like to mention that our institution has received the approval of ourethics committee and the Drugs Controller General (India) has permitted us toconduct the trial. The trial is being conducted under strict conformance to theICMR and guidelines for good clinical practice.

I would be extremely pleased to answer any questions you may have.

Dr J BiswasHead of the Department of Ocular-Pathology and UveitisMedical and Vision Research FoundationsSankara Nethralaya, 18, College Road, Chennai - 600 006Phone: 044-8271616, Extn. 1302 / 1719Fax : 044-8254180E-mail: drjb@sankaranethralaya.org

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UPDATE IN NEURO-OPHTHALMOLOGYOrganized by

Medical and Vision Research Foundations, Sankara NethralayaOctober 26 & 27, 2002 at Hotel Ambassador Pallava, Chennai

The update will include lectures, discussion, and case presentations on following topics:The optic nerve and its disorders, The efferent visual system, Neuroradiology and

trauma, Ocular myopathies and Tumours of neuro-ophthalmic interest.

FACULTYDr. Robert Daroff, Cleveland, Ohio, USADr. Andrew Lee, Iowa City, Iowa, USADr. JF Cullen, SNEC, SingaporeDr. Sharon Tow, SNEC, SingaporeDr. Avertano Noronha, Chicago, USADr. Vimala Menon, RP Centre, DelhiDr. G. Natchiar, Aravind Eye Hospitals,

MaduraiDr. G. Arjundas, ChennaiDr. Deepak Arjundas, ChennaiDr. Suresh Bapu, Chennai

Registration feeDelegates – Rs. 1000/-

For Postgraduates - Rs. 500/-(should attach a letter from the head of their institution

certifying their postgraduate status)Last date - August 15, 2002 (No spot registration)After 15th August: Rs. 1500/- for delegates and

Rs. 1000/- for postgraduates

ContactDr. Satya Karna, Organizing secretary

Medical and Vision Research Foundations18 College Road, Chennai 600006, IndiaPhone: 8271616, 8261260, 8261265, 8271036

Fax: 91-044-8254180/ 8210117Email: drsk@sankaranethralaya.org

neurocme@lycos.com

Please send the demand draft in favor of“Medical Research Foundation”

along with your name, designation, specialty, address,contact telephone, fax and email.

Online registration atwww.sankaranethralaya.org/ophthal_events1.htm

Dr. B. Chidambaram, ChennaiDr. Veena Noronha, ChennaiDr. Swatee Halbe, ChennaiDr. Sujatha, ChennaiDr. K. Ganapathy, ChennaiDr. K. Rajaram, ChennaiDr. K.C. Parvatham, ChennaiDr. A. Gajaraj, ChennaiDr. Thulasi Das, ChennaiDr. D. Rout, ChennaiSankara Nethralaya faculty

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ABSTRACTSince rapid aetiological diagnosis of viral

retinitis is essential for institution of specifictherapy, we evaluated the role of polymerasechain reaction (PCR) against fluorescentantibody technique (FAT) on intraocularspecimens. One hundred and thirty intraocularspecimens from 111 patients were investigatedfor herpes simplex virus (HSV), varicella zostervirus (VZV) and cytomegalovirus (CMV) by FATand PCR. FAT alone detected the presence ofHSV, VZV or CMV in five (3.8%) specimensfrom five (4.5%) patients, FAT and PCR in six(4.6%) specimens from four (3.6%) patientsand PCR alone in 72 (55.4%) specimens from66 (59.5%) patients. PCR has increased theclinical sensitivity by 55.4% and 59.5% amongthe specimens and patients respectively, whichwas statistically significant (McNemar test,P<0.001). We conclude that PCR is a rapid,absolutely specific, several folds sensitive anda more reliable diagnostic tool than FAT inviral retinitis.Key words: Polymerase chain reaction, Viralretinitis, Herpes simplex virus, Varicella zostervirus, Cytomegalovirus

INTRODUCTIONHerpetic retinal and choroidal diseases

is a problem encountered in both immuno-competent and immunosuppressed patients, butpresents a greater diagnostic dilemma in theformer group because of a low index ofsuspicion.1 Accurate differentiation of herpessimplex virus (HSV) and varicella zoster virus(VZV) from cytomegalovirus (CMV) hassignificant therapeutic implications, as thetherapeutic agents differ.2 In the early stagesof ocular manifestations and in patients withatypical features, it is difficult to differentiate

Diagnostic value of polymerase chain reaction(PCR) on intraocular specimens from patientswith viral retinitisK Priya, J Malathi and H N Madhavan

between CMV and other herpesvirus associatedretinitis. Discrimination between viral and non-viral pathogens such as Toxoplasma gondii canbe particularly difficult solely based on clinicalpresentations.2 Rapid and accurate diagnosisof the ocular infection and prompt initiation ofappropriate therapy is essential both for thepreservation of sight and improved survival ofthe patient.3 Furthermore, the personal cost ofthe patient and the wastage of resourcesassociated with the use of multiple antiviraltherapies prompts the development of rapid,sensitive and specific diagnostic tests for ocularpathogens.4 The conventional laboratorymethods of virus diagnosis include antigendetection by fluorescent antibody test (FAT)and virus isolation. Virus isolation, though thegold standard, is not a rapid diagnosticmethod. FAT, though rapid is adverselyinfluenced by small sample size and low antigenthreshold. Polymerase chain reaction (PCR) hasbeen employed as a molecular biological toolin the diagnosis of viral retinitis by manyinvestigators.2,5,6 Therefore we evaluated therole of PCR in the aetiological diagnosis ofherpesviral retinitis.

MATERIALS AND METHODSPatients and specimens

A total of 130 (104 aqueous humor [AH],26 vitreous fluid [VF]) intraocular specimenswere collected from 111 patients during aperiod of 3 years from 1999-2001. The 111patients included 32 acute retinal necrosis[ARN], six progressive outer retinal necrosis[PORN], 23 CMV retinitis, two herpes zosterophthalmicus [HZO], 13 geographic hellicoidperipapillary choroiditis [GHPC], 17 viralretinitis, three choroiditis, 13 uveitis, oneretinal vasculitis, one retinal sclerosis. Of the

18

111, 24 patients were humanimmunodeficiency virus (HIV) positive. BothAH and VF were collected from 14 patients.

ControlsNinety intraocular fluids (30 AH from

cataract extractions, 20 VF from patients withdiabetic retinopathy, 20 AH and 20 VF fromculture proven bacterial or fungalendophthalmitis) collected from 90 patientswere included as controls to determine theprevalence of herpesviral DNA in the intraocularfluids of patients without clinical evidence ofan active viral inflammatory process.

Fluorescent antibody test (FAT)Fluorescent antibody test (FAT) was done

using rabbit polyclonal anti-HSV types 1 or 2antisera for HSV, hyperimmune antisera forVZV and mouse monoclonal anti-CMVantisera.3,7

Polymerase chain reaction (PCR)DNA extraction and PCR were carried out

as described by us earlier.8,9 In brief, the DNAwas extracted by proteinase K - phenolchloroform method. PCR was done usingcustom synthesized primers coding for theDNA polymerase gene of HSV, the immediateearly gene 63 for VZV and the morphologicaltransforming region II gene for CMV. The PCRreagents were procured from Bangalore GeneiPvt. Ltd. (Bangalore, India) and theamplification was carried out in Perkin Elmer

model no. 480 and 2400 (USA) and HybaidOmnigene model no. HBTR3CM (UK). The PCRamplified products were analyzed by gelelectrophoresis using 2% agarose containing0.5 g/ml of ethidium bromide.

The specificity of the primers was testedusing various viral, bacterial and fungal DNA,human DNA and the intraocular control DNA.The sensitivity of the primers was tested usingserial 10-fold dilutions of the correspondingpositive control DNA of HSV, VZV and CMV.

ResultsThe primers targeting HSV, VZV and CMV

were absolutely specific, as they did not amplifyany of the other viruses, bacteria, fungi orhuman leukocyte DNA. The sensitivity of thePCRs was 0.2 pfu/ml and 0.3 pfu/ml for HSV-1 and HSV-2 respectively, and 10fg and onefemtogram for VZV and CMV respectively. PCRdid not detect HSV or CMV genomes in any ofthe 90 intraocular control fluid samples. VZV-DNA was detected in 1 (1.1%) of 90 controlsamples, which was a VF from a cultureproven case of bacterial endophthalmitis.

The specimen-wise and patient-wiseresults of FAT and PCR for the detection ofHSV, VZV and CMV on 130 specimens from111 patients have been tabulated in tables 1and 2 respectively. Of the 130 specimens from111 patients, FAT alone detected the presenceof HSV, VZV or CMV in five (3.8%) specimensfrom five (4.5%) patients, FAT and PCR in six

Table 1: Specimen-wise results of fluorescent antibody test (FAT) and polymerasechain reaction (PCR) for the detection of herpes simplex virus (HSV), varicella zoster

virus (VZV) and cytomegalovirus (CMV) in 130 intraocular specimens from 111patients with viral retinitis

HSV VZV CMV S No Specimen No. of

specimens FAT+ FAT/ PCR+ PCR+ FAT+ FAT/

PCR+ PCR+ FAT+ FAT/ PCR+ PCR+

1 AH 104 1 - 12 2 2 25 - - 17

2 VF 26 - 2 4 2 2 4 - - 10

Total 130 1 (0.8) 2 (1.5) 16 (12.3)* 4 (3.1) 4 (3.1) 29 (22.3)* - - 27 (20.8)*

Numbers in parenthesis denotes the percentage

AH - aqueous humor; VF - vitreous fluid

* - PCR has increased the clinical sensitivity by 55.4% which was statistically significant (McNemar test, P<0.001)

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(4.6%) specimens from four (3.6%) patientsand PCR alone in 72 (55.4%) specimens from66 (59.5%) patients. Thus PCR has increasedthe clinical sensitivity by 55.4% and 59.5%among the specimens and patientsrespectively, which was statistically significant(McNemar test, P<0.001).

Of the 14 patients with dual specimensof AH and VF, herpesviral DNA was detectedin AH alone in one (7.1%), VF alone in five(35.7%) and both in five (35.7%) patients.Overall, herpesviral DNA was detected in 56(52.8%) of 106 AH and 22 (84.6%) of 26 VF.

DiscussionIn 1995, before the introduction of PCR,

we implicated herpesviral aetiology in 44.4%of ARN patients (2 HSV and 2 CMV) by FAT.3In 1999, we implicated herpesviral aetiologyin 18.8% of ARN patients (1 HSV 2 VZV and3 CMV) by FAT.10 Today in this study, theherpesviral aetiology was implicated by FAT in3.6% of viral retinitis patients. This decreasein the antigen detection rate by FAT over the

years is probably attributed to the decreasingantigen threshold due to the high load ofantivirals before the patients reach the referralcentres. With the application of PCR herpesviralaetiology was implicated additionally in 59.4%of these patients. This implies the remarkableincrease in the rate of aetiological diagnosis ofviral retinitis. In five specimens from fivepatients, HSV or VZV antigens were detectedby FAT alone while their corresponding genomeswas not detected by PCR. This positivity wasconsidered as false due to the high relativesubjectivity of the microscopic observationsinvolved in the interpretation of fluorescencetests. This was further confirmed by theexclusion of the presence of PCR inhibitors inthese specimens by spiking them with theleast amount of known positive control DNA.

PCRs for the detection of HSV, VZV andCMV were absolutely specific and highlysensitive. VZV-DNA was detected in one patientwith post-operative bacterial endophthalmitis.It is likely that in this patient activation ofVZV could have been triggered during the

Table 2: Patient-wise results of fluorescent antibody test (FAT) and polymerase chainreaction (PCR) for the detection of herpes simplex virus (HSV), varicella zoster virus

(VZV) and cytomegalovirus (CMV) in 130 intraocular specimens from 111 patients withviral retinitis

HSV VZV CMV S. No Clinical diagnosis No. of

patients FAT+ FAT/ PCR+ PCR+ FAT+ FAT/

PCR+ PCR+ FAT+ FAT / PCR+ PCR+

1 ARN 32 1 1 8 3 2 9 - - 5

2 PORN 6 - - - - - 2 - - 3

3 CMV retinitis 23 - - 1 - - 2 - - 13

4 HZO 2 - - - - - 1 - - -

5 GHPC 13 - - 2 1 - 5 - - -

6 Viral retinitis 17 - - 2 - - 5 - - 2

7 Choroiditis 3 - 1 - - - 1 - - 1

8 Uveitis 13 - - 1 - - 1 - - 1

9 Retinal vasculitis 1 - - 1 - - - - - -

10 Retinal sclerosis 1 - - - - - - - - -

Total 111 1 (0.9) 2 (1.8) 15 (13.5)* 4 (3.6) 2 (1.8) 26 (23.4)* - - 25 (22.5)*

Numbers in parenthesis denotes the percentage* - PCR has increased the clinical sensitivity by 59.5%, which was statistically significant (McNemar test, P<0.001)

20

episode of bacterial endophthalmitis with a spillover of the virus-laden leukocytes into thevitreous cavity. The absence of HSV, VZV andCMV genomes in the intraocular fluids ofpatients undergoing cataract extraction andpatients presenting with non-viral retinalinflammations indicate that the detection ofherpesvirus DNA by PCR implicates an activeinfection. Other investigators have also shownsimilar findings,5,11,12 except in one report byFox et al6 who detected CMV-DNA in one ofeight vitreous fluid tested from normal persons.

Comparing the detection rate of AH andVF, our findings indicate that AH is as good asVF in the detection of the herpesviral aetiology.Therefore, being a simple and safe officeprocedure, AH is an ideal specimen for thedetection of the viral aetiological agent by PCR.

In the context of an established diagnosticvirology laboratory in India, the approximateworking (recurring) cost to detect these threeviruses per specimen of conventional virologicalmethods (FAT and virus isolation) is Rs. 1200/- while that of PCR is Rs. 750/-. The expertiseof the personnel involved is equally expensivefor both the tissue culture and PCR work.

In this study we have been able toattribute herpesviral aetiology in 72/113(63.7%) patients with viral retino-choroiditis.Thus, PCR has been extremely helpful as arapid, absolutely specific, highly sensitive anda more reliable diagnostic tool for the detectionof the herpesviral agents in patients with viralretinitis.

References1. Culbertson WW. Viral retinitis. In:

Infections of the eye, 2nd ed. Tabbara KFand Hynduik RA, Eds Little, Brown andCompany, New York, 1986; p 499-510.

2. Yamamoto S, Langston DP, Kinoshita S,Nishida K, Shimomura Y, Tano Y. Detectingherpesvirus DNA in uveities using thepolymerase chain reaction. Br JOphthalmol 1996; 80: 465-468.

3. Madhavan HN, Biswas J, Gopal L, SharmaT. Investigations in the virological etiologyin acute retinal inflammation. Indian J MedRes 1995; 101: 233-237.

4. Mitchell S. Diagnostic assays incytomegalovirus retinitis. Br J Ophthalmol1996; 80: 195-196.

5. Mitchell SM, Fox JD, Tedder RS, GazzardBJ, Lightman S. Vitreous fluid samplingand viral genome detection for thediagnosis of viral retinitis in patients withAIDS. J Med Virol 1994; 43: 336-340.

6. Fox GM, Crouse CA, Chuang EL,Pflugfelder SC, Cleary TJ, Nelson SJ,Atherton SS. Detection of herpesvirus DNAin vitreous and aqueous specimens by thepolymerase chain reaction. ArchOphthalmol 1991; 109: 266-271.

7. Minnich LL, Smith TF, George C. In: Rapiddetection of viruses by immuno-fluorescence. Cumitech 24, WashingtonDC: American Society for Microbiology,1988; p 1-13.

8. Madhavan HN, Priya K, Anand AR, LilyTherese K. Detection of herpes simplexvirus (HSV) genome using polymerasechain reaction (PCR) in clinical samples.Comparison of PCR with standardlaboratory methods for the detection ofHSV. J Clin Virol 1999; 14: 145-151.

9. Priya K. Application of rapid aetiologicaldiagnostic methods on intraocularspecimens in viral retino-choroiditis. IndianJ Med Microbiol 2001; 19: 14-19.

10. Madhavan HN. Laboratory investigationson viral and Chlamydial trachomatisinfections of the eye: Sankara Nethralayaexperiences. Indian J Ophthalmol 1999;47: 241-246.

11. Fenner TE, Garweg J, Hufert FT, BoehnkeM, Schmitz H. Diagnosis of humancytomegalovirus-induced retinitis in humanimmunodeficiency virus type 1-infectedsubjects by using polymerase chainreaction. J Clin Microbiol 1991; 29: 2621-2622.

12. Pendergast SD, Werner J, Drevon A,Wiedbrauk DL. Absence of herpesvirusDNA by polymerase chain reaction inocular fluids obtained fromimmunocompetent patients. Retina 2000;20: 389-393.

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We have been confronted with the"difficult patient" many a time and we havefound it worth while helping both patient andsurgeon under such circumstances.

CLAUSTROPHOBIA & SUFFOCATIONThe patient suffering from claustrophobia

refuses to be draped after administration ofthe local anaesthetic. If we are aware that thepatient suffers from claustrophobia we try a"trial draping" pre-operatively after explainingto the patient the manner in which he will bedraped in the operation theatre. It helps toask the patient how he feels with the drapescovering his face. If the patient feelsuncomfortable we lift up the drape from theface and give sufficient space till the patientfeels comfortable.

We have also asked the patient's relativesto try draping the patient at home. This isespecially useful in the mentally retardedpatient (eg. The patient with Down'sSyndrome.)

On the operation table also we try thesame technique providing the patient withenough space by lifting the drapes away fromthe face. We use a special stainless steel archthat is placed across the patient's chest whichhelps to lift the drapes preventing them fromfalling on the patient and causing a feeling ofsuffocation. This also gives enough room forthe patient to breathe easily.

Oxygen is administered via a twin borenasal oxygen catheter and the flow may beincreased till the patient feels comfortable.Sometimes allowing sufficient light to enterunder the drapes seems to help theclaustrophobic patient.

A patient undergoing ophthalmic surgeryunder local anaesthesia may become unco-operative after entering the operation theatredue to "needle phobia" or may pull out thesterile drapes after being draped, due tosuffocation or claustrophobia.

Sometimes it is possible to assuage thefears of the unco-operative, anxious patient andconvince him to undergo surgery under localanaesthesia. In the occasional patient however,it may be necessary to reassess the patient'sfitness to undergo a general anaesthesia andreturn for surgery at a later date.

General anaesthesia has its owndisadvantages when compared with a local ora regional anaesthesia. Furthemore, severalpatients who present for cataract surgery haveco-existing medical diseases like ischaemicheart disease, hypertension, diabetes, asthma,liver, renal or endocrine disease. Specialinvestigations such as an echocardiogram orserum electrolytes may also be required andthis may further delay surgery.

Local anaesthesia acts by blocking painsensation without producing totalunconsciousness. There is less 'insult' to thevarious systems and less release of stresshormones.1 The problems of postoperativenausea and vomiting, laryngospasm and othercomplications related to general anaesthesiacan also be avoided.

Sometimes patient's relatives are unwillingfor a patient to undergo the risk a generalanesthesia for cataract surgery. So left with nochoice a local anaesthesia will have to given.

How can you convince a patient to co-operate and help him to overcome his fear ofneedles, suffocation and claustrophobia? Howto convince him to stay still during surgery ?Is it possible ?

Managing the unco-operative patient underLocal Anaesthesia - How We Do ItIan Sundararaj

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DEMENTIA

Alzheimer's DiseaseAfter obtaining intravenous access (which

can sometimes prove difficult!), the patientmaybe sedated with midazolam2 ( a short actingbenzodiazepine) in the dose of 1mgintravenously and propofol3 (a short actingintravenous agent) given in 10mg incrementaldoses. After the patient is just asleep and quiet,the local anaesthetic block is given. Recoveryfrom propofol is quick and uneventful.4

ANXIETY, APPREHENSIONInjection midazolam in a dose of 0.5 -

1mg intravenously followed by propofol in 10mg incremental doses have both been tried withsuccess in many of our patients. Propofol canbe used in intermittent doses till the patientis made calm but is still conscious andresponding to commands.

The patient recovers completely andquickly soon after the last dose.

We have found it helpful to allow thepatient's close relative to be with the patientin the operation theatre to hold his handduring surgery and talk to him.

INTERSTITIAL LUNG DISEASE,COPD, KYPHOSCOLIOSIS

Patients with chronic lung disease will findit difficult to lie supine for long periods oftime. A careful detailed history will be helpfulto ascertain the correct position in which thepatient can lie comfortably without anyrespiratory insufficiency. The position in whichthe patient sleeps at night,( eg. supported bypillows etc) maybe tried on the operating table.After positioning the patient the surgeon shouldfocus the operating microscope and see if he isable to perform surgery in a position other thanthe usual. The patient should be supportedusing a pillow to maintain that posture withoutmoving.

HARD OF HEARINGIf the patient is hard of hearing and does

not use a hearing aid and if he has some vision

in the eye he is shown the syringe, needle etcand using hand signs the local anaestheticprocedure is explained to the patient.

When the surgery is over and when weremove the drapes we often find a smilingsatisfied face filled with gratitude!

UNDERSTAND THE PATIENT'S PROBLEMSome times the patient may have

problems which could be the cause forrestlessness such as a distended bladder,water entering the ear while cleaning, severeback pain or pain in the leg, tight BP cuff etc.In such situations the cause should beascertained and appropriate measures takento alleviate the patient's discomfort.

These are some of the simple butimportant measures by which we have beenable to successfully anaesthetize and operateon our patients.

REFERENCES1. T. Heurmann, T.Yousif, Anders, C

Hartmann Stress response during cataractsurgery in Local Anaesthesia - Peribulbarversus Intracameral lidocaine injection.97th DOG Annual Meeting, 1999

2. Kost M, Emerson D Propofol - fentanylversus Midazolam - fentanyl: acomparative study of local sedationtechnique for cataract surgery .CRNA1992;3:7-15

3. Holas A, Faulborn J. Propofol versusDiazepam for sedation of patientsundergoing ophthalmic regionalanaesthesia. Anaesthetist 1993; 42:766 -772

4. Zurmond WW, Van Leewen L, Helmers JHRecovery from propofol infusion as themain agent for outpatient arthroscopy. Acomparison with isoflurane. Ann FrAnaesth Reanim 1987:6(4):309 -12

5. Short TG, Chui PT Propofol and Midazolamact synergistically in combination. Br. JAnaesth 1991; 67:539 -45

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Tests for toxoplasmosis were repeatedand were again found to be negative.

The patient was being followed up on aregular basis here and complained of fluctuatingvision in both eyes. At his last checkup here,his visual acuity was 6/24; N10 and 6/60;N10 in both eyes. Clinically the extent of theatrophic fundus lesion was the same; howeverthe pigmentation within the lesion was foundto be progressively increasing.

Electroretinogram test carried out inFebruary 1999 showed marked reduction inboth the cone and rod responses, indicating amore generalized involvement of the retina. Thetest repeated two years later showed furtherreduction in the rod and cone responses.

Color vision was found to be grosslyaffected as tested with Ishihara's test plates.

Examination of the patient's brothershowed similar fundus lesions.

Case 2 : A 35-year-old female patientpresented with history of decreased vision andnystagmus in both eyes since early childhood.Vision was more or less stable and the patientdid not complain of progressive loss of vision.Past and family history was unremarkableexcept for history of consanguinity amongsther parents. She gave history of having scantyhypopigmented hair since early childhood. Herbest-corrected visual acuity was noted to be 3/60;N6 in both eyes. A refractive error of -11.0Dsph and -9.00 Dsph was noted in the rightand left eye respectively. Fundus examinationin both eyes showed mild pallor of the opticnerve head. A broad annular atrophic ring wasnoted in the central macular region. Rest ofthe posterior pole had a tessellated appearance.The retinal blood vessels and the peripheralretina were normal. Fluorescein angiographyshowed a central annular band of transmission

INTRODUCTIONAmino acids are known to be associated

with retinal degenerative disorders. Hyperhomocystinuria is associated with retinal veinocclusion1. Ornithinemia is seen in patientswith gyrate atrophy2. Few cases of glycinuria3

and cystinuria4 have also been reported to beassociated with retinal degenerative diseases.Hyperthreoninemia is associated withblindness, nystagmus and variableopthalmoscopic appearance4. In this articlewe report for the first time the association ofmacular abnormalities seen in patients withelevated levels of histidine.

CASE REPORTSCase 1 : This patient was first seen here

in 1981 as a 7-year-old child who was broughtfor examination with complaints of defectivevision in both eyes and squinting of eyes. Atthat time he was noted to have scanty,hypopigmented scalp hair. The antenatalhistory was unremarkable. He was born of afull term, forceps assisted delivery. There wasno history of any birth injuries. His youngerbrother was having similar complaints. Historyof consanguinity was noted amongst theparents. The child had undergone investigationsto detect antibodies against toxoplasmosis -the tests were negative. X-ray of the skullhad been done elsewhere and was normal.

His best-corrected visual acuity wasnoted to be 6/18; N 6 and 6/18; N 18 in theright and left eye respectively. A refractivecorrection of -1.75 diopter spherical wasrequired in both eyes. Fundus examinationin both eyes showed a large well-demarcatedatrophic lesion involving almost the entiremacula. Pigment clumping was noted withinthe lesion. The optic nerve head and theretinal blood vessels were normal.

Macular Changes associated withHyper HistidinemiaNitin S Shetty, S. Lakshmi and K. N. Sulochana

24

defect. An ERG test showed reduction in boththe rod and the cone amplitudes.

BIOCHEMICAL METHODS:

Amino acid and homocystine analysis inplasma sample was done in acid citratedextrose anticoagulated blood sample andfasting urine sample. The clear supernatantobtained after precipitating the plasma with10%TCA was used for the analysis.

The amino acid analysis was carried outusing HP-HPLC by the method of pre-columnOPA derivatization. The detection was carriedout at 338nm using variable wavelengthdetector. The gradient elution was performedusing acetate buffer (A) and acetate bufferwith 40% of acetonitrile and methanol each(B) of pH 7.25.

Homocystine analysis was performedisocratically using phosphate buffer of pH 3.5with C18 RP column and the detection wasdone at 190 nm (UV detector)6.

RESULTS & DISCUSSIONThe amino acid analysis revealed increase

in plasma histidine. In case 1 it was 106.56and in case 2 - 60.05. (normal 26.34 ± 3.98)nm/ml and normal levels of other amino acidsin both plasma and urine. In case 2, thehomocystine was found to be increased to50µM from a normal of 0-19µM in urine andnormal levels in plasma.

Histidine, an imidazole containing aminoacid is catabolised to glutamate and in thisprocess, it contributes a carbon atom to onecarbon metabolism. The enzyme involved ishistidase. An error in this metabolism leads toincrease in histidine levels leading tohistidinemia. This is a rare genetic disorderthat is inherited in an autosomal recessive7

pattern. Histidinemia cases often have impairedintellectual speech development. However ourcases appeared to be intelligent. In one of thearticle published by the Dhir SP etal havereported the association of histidinemia8 withreduced visual acuity, nystagmus andhypopigmentation of the maculae. In our casesalso we have similar clinical findings liketypical RPE degeneration, reduced visualacuity and hypopigmentation of hair etc.

The mechanism behind histidinemia maybe due to a disorder in the enzyme histidase.The disorder or deficiency of histidase enzymemay be due to a mutation in the gene codingfor the protein histidase . This enzyme isnecessary for the conversion of histidine totransurocanic acid. This intermediate productis reported to undergo photoisomerisationwhen it absorbs UV light. It is also believedthat the enzyme histidase has a role inmediating UV protection via the transurocanicacid. Thus when there is impairment in theenzyme histidase, there may be possibility ofhypopigmentation in the patients withhistidinemia9.

Fundus photography of Right {A} and Left {B} Eye of Case 1

25

Alternatively the cause of histidinemia maybe due to deficiency of vitamin folate that isinvolved in the histidine metabolism. It issuggested that for such patients intake ofvitamins or plenty of vegetables and fruitswith low histidine diet can be given.

In case 2 an increase in homocystine inurine along with histidinemia was observed.The increase in level of homocystine isreported to be a marker for the diagnosis ofthe deficiency of vitamin B12 and folate10.Homocystinemia is also reported to be a riskfactor for nonarteritic anterior ischemic opticneuropathy, central retinal artery occlusion

and central retinal vein occlusion11. Thisdeficiency may also be due to defectiveabsorption or availability of the vitamins.

Even though both conditions had changesrestricted to the posterior poles, thecharacteristics of the lesions were quitedifferent. Factors other than just histidineabnormality may be playing a role. These needto be further investigated. The ERG findings inboth cases were however more or less similarwith marked reduction in both the cone androd responses. Progressive loss of the ERGamplitudes as seen in Case 1 suggests thatthis is likely to be a progressive condition.

Fig : 1 Plasma Amino acid profile from a Normal individual

Plasma Histidine level : 30.32 (normal : 26.34 ± 3.98)

Fig : 2 Plasma Amino acid profile of case 1 with Macular changes

Plasma Histidine level : 102.56 (normal : 26.34 ± 3.98)

26

4. Seiji Hayasaka, Satoshi Hara, KatsuyoshiMizuno, Kuniaki Narisawa and Keiya Tada.Leber's Congenital Amaurosis Associatedwith hyperthreoninemia. American Journalof Ophthalmology. 1986;101:475-479.

5. Angelika Gratzfeld-Hesgen. Sensitive andReliable Amino acid analysis in proteinhydrolysates using the HP 1100 seriesHPLC. (Technical Note: Hewlett Packard).

6. Elizabeth Jayatilleke and Spencer Shaw.A high-performance liquid chromatographicassay for reduced and oxidized glutathionein biological samples. AnalyticalBiochemistry. 1993;214:452-457.

7. Rodwell VW Catabolism of the CarbonSkeletons of Amino Acids In: Harper'sBiochemistry 23rd edition; 1993:305.

8. Dhir SP, Shisku MW, Krewi A. Ocularinvolvement in histidinaemia. OphthalmicPaediatr Genet 1987;8(3):175-176.

9. Taylor RG, Grieco D, Clarke GA, McinnesRR and Taylore BA. Identification of themutation in murine histidinemia andgenetic mapping of the murine histidaselocus on chromosome 10. Genomics1993;16:231-240.

10. Dierkes J, Kroesen M, Pietrzik K., Folicacid and Vitamin B6 supplementation andplasma homocysteine concentrations inhealthy young women, Int J Vitam NutrRes 1998; 68(2) : 98-103.

11. Pianka P, Almog Y etal.Hyperhomocystinemia in Patients withNonarteritic Anterior Ischemic OpticNeuropathy, Central Retinal ArteryOcclusion, and Central Retinal VeinOcclusion. Opthalmology 2000; 107 :1588-1592.

The mode of inheritance in these patientscould not be exactly determined. The historyof consanguinity in the parents in both thecases could suggest a autosomal recessiveinheritance. However the other familymembers need to be examined both clinicallyand by biochemical tests, in order to detectany 'subclincal' cases.

In the 2 cases we have reported theincrease of histidine is association with theclinical findings of macular dystrophicchanges. In such cases of macular dystrophy,the measurement of plasma amino acid. -histidine in particular, may be useful in thedifferential diagnosis. Readymade diet low inhistidine may be used with regular monitoringof histidine levels in blood and urine.

REFERENCES1. Valerie Biousse, Nancy J.N and Paul

Sternberg. Retinal vein occlusion andtransient monocular visual loss associatedwith hyperhomocystinemia. AmericanJournal of Ophthalmology 1997;101:475-479.

2. Takki K and Simell O. Gyrate Atrophy ofthe Choroid and Retine withHyperornithinemia. In The Eye and InbornErrors of Metabolism. Bergsma D, BronAJ and Cotlier E editors. Alan R Liss, Inc.,Newyork.373-384.

3. Seiji Hayasake, Katsuyosh Mizuno,Kazuyuki Yabata, Takashi Saito and KeiyaTada. A typical Gyrate atrophy of thechoroid and retina associated withiminoglycinuria. Arch Ophthalmol1982;100:423-425.

INSIGHT & EYELIGHTS are now available on line athttp://www. sankaranethralaya.org/publication.htm

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microscope to record intra-operativephotographs. The camera can also be used totake photographs of CT Scan, MRI, X Rayplates attached to the view box. Some of thesecameras also have a facility to record videofor a short duration besides still photographs.This also is useful to record observationssuch as nystagmus, essential blepharospasm,etc. Attached to the slit lamp one can alsorecord procedures such as tear film break uptime, siedel's test for leaking wounds etc.

AN APPEALAN APPEALAN APPEALAN APPEALAN APPEALA lot of things in this world depend on money - security, shelter, education and evenhealth. But at Nethralaya, money has ceased to be a pre-requisite for sight.Day after day, year after year, Nethralaya treats hundreds of patients absolutely freeof cost and gives them back their sight. Treatment is provided free of cost to allpatients with a monthly income below Rs.1,750/-.Yet there is no discrimination between the free patient and the one who pays. Apartfrom the treatment, food, medicines and travel expenses are absolutely free.Those free patients depend on Nethralaya, and Nethralaya depends on you.So, come and join the OPHTHALMIC MISSION TRUST.For questions about tax exempt status and contributions, please contact:

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For those of you in India and elsewhere, please contact:Dr S S Badrinath,

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Which camera to buy ? Well there areseveral cameras available in the markettoday.(Nikon, Kodak, Sony, Canon, Fuji,Minolta) Most of these cameras are pricedbetween 600 to 800 US $. One should choosea camera that gives a minimum resolution of2 million pixels. This is essential to haveprintouts comparable to standardphotographic quality. The Nikon coolpix 995with a resolution of 3.34 million pixels is agood buy and proves useful in ophthalmicphotography.

(contd. on page 28)

Editor : Dr. Rajesh Fogla 28

For Private Circulation Only

(contd. on page 27)

Last Page

Digital PhotographyRajesh Fogla

1536 pixels. This is essential for good qualitycolour prints. How are the images stored ? Wellthe images are instantly stored onto the harddisk or memory card in the camera. Compactflash card of different storage capacity areavailable (16 / 32/ 64 / 128 Mb) and thenumber of pictures it can store depends on theresolution selected. These images can betransferred to the computer and stored oncompact discs. The images can also be viewedon the large screen of the computer monitor.

Digital workstations though expensive,provide a variety of options for ophthalmicphotography. The images taken can beimmediately reviewed on the large monitor atdifferent magnifications. Various imageenhancement techniques can also be appliedto these images. The images can be stored ortransferred to a different computer over thenetwork.

Photography with the handheld digitalcamera is fairly simple. Most of the images canbe taken in the autofocus mode. These imagescan be instantly reviewed on the inbuiltmonitor of the camera and taken again if notsatisfactory. External macrophotographs of theeye and adnexa are easy to shoot in ambientroom illumination. Slit lamp photography ofthe anterior segment needs a little patienceand practice. The camera lens needs to beheld or attached to the eyepiece of the slitlamp. Excellent photographs can be takenwith diffuse illumination, slit illumination andretroillumination. One can also attach thecamera to the eyepiece of the operating

Photographic documentation is anessential component of clinical ophthalmology,to document interesting cases, assess treatmentoutcomes and collect data for teaching andresearch. It has played a crucial role in manysuccessful research projects to determine theeffectiveness of newer treatment procedures, toobtain knowledge about eye diseases and theireffect on vision. It also proves useful as ateaching tool, to describe various oculardiseases to residents in training, as well asophthalmologists at various continuingmedical education sessions.

Majority of the clinical imaging inophthalmology is related to the posteriorsegment ie retinal photography and fundusfluorescein photography. This is followed byexternal photography of the eye and adnexa,and slit lamp photography of the anteriorsegment.

Most of these photographs are usuallytaken with the conventional 35mm camera withmacrolenses of long focal length, and electronicflash equipment. With recent advances intechnology, many sophisticated products usingcomputers and imaging technology are currentlyavailable in the market for ophthalmicphotography. These latest digital cameras offermany advantages over the standard 35 mmequipment, and allow instant availability ofresults besides adjustment of image parameters.

Digital cameras have a chip or CCD thatimages the photograph. A digital camera witha high density 3.34 million pixels CCD chip,gives a maximum image resolution of 2048 x

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