3
three months or less with focal central distortion noted on the Amsler grid. All patients did not see a break in a thin slit beam placed across the lesion (negative Watzke-Allen sign) on initial evaluation. Patients underwent a complete ophthalmologic examination, best corrected Snellen visual acuity, fundus photographs, and fluorescein angiography. Exclusion factors included high myopia over 6.5 diopt- ers, myopic macular degeneration, diabetic retinopathy, or age related macular degeneration. Most stage I holes were initially observed, but then managed in three groups: (I) observation only, if spontaneous resolution developed 7 eyes; (II) pars plana vitrectomy, posterior cortical vitreous separation, and fluid 20% sulfur hexafluoride gas ex- change if vision worsened to 20/50 or worse with a stage I hole configuration 9 eyes; (III) pars plana vitrectomy, posterior cortical vitreous peeling, membrane peeling without internal limiting membrane peeling, fluid 18% perfluoropropane gas exchange for acute full-thickness hole (stage II or III) 9 eyes. All patients had at least six months and up to nine years of follow-up. During observation (group I) spontaneous resolution developed in 7 eyes with all maintaining 20/40 or better vision. Presenting vision in group I was 20/40 or better in 5 eyes. Two patients with presenting vision of 20/60 to 20/70 elected to observe and spontaneously resolved. Spontaneously resolved holes often showed a focal foveal facet, similar to postoperative cases. In group II following vitrectomy and fluid-gas exchange with sulfur hexafluoride, 8 of 9 eyes did not progress and recovered 20/40 or better vision (Figure 1, right). One of 9 eyes required a subse- quent surgery with perfluoropropane after macular hole progression, but recovered 20/40 vision with hole closure. In 9 eyes which acutely progressed from stage I to a full-thickness hole (group III), pars plana vitrectomy, posterior cortical vitreous separation, membrane peeling, and fluid-gas exchange with perfluoropropane resulted in hole closure in all eyes, and recovery of 20/40 or better vision. Of the 9 eyes in group II, one was previously pseudophakic, two developed moderate cataracts, and six underwent cataract surgery. Of the 9 eyes in group III, two were previously pseudophakic, one had a mild cataract, and six underwent cataract surgery. One of 18 operated eyes (5%), an eye in group II, developed retinal detach- ment with reopening of the macular hole, but recovered 20/20 vision with surgical repair. Resolution of macular hole in the acute stages of development allowed excellent anatomic and visual results in all three groups. All 25 patients recovered 20/40 or better vision at last follow-up. Stage I holes with poor vision (group II) progressed in 12% (1/9 eyes) following vitrectomy with gas tamponade, which compares favorably with the natural history of stage I macular holes with vision of 20/50 or worse (66% progression rate). 4 This also compares favorably with the vitrectomy group in the Vitrectomy for Prevention of Macular Hole Study (37% progression rate), 1 which did not include intraocular gas tamponade and whose progression rate may have been even higher if limited to high risk eyes with poor vision. 4 However, this present study is a retrospective and nonran- domized study with small numbers in each group. In addition, the risks of post-vitrectomy cataract formation and occasional retinal detachment must be weighed against the potential benefit of better vision potential with earlier intervention. Observation was recommended ini- tially in most cases, and is especially recommended for stage I holes with best corrected visual acuity of 20/40 or better due to the low progression rate. 4 A randomized clinical trial studying vitrectomy with intraocular gas tamponade in stage I holes with poor vision versus inter- vention only after full-thickness hole development is indicated and may be aided by the use of optical coherence tomography for patient selection. REFERENCES 1. De Bustros S. The Vitrectomy for Prevention of Macular Hole Study Group. Vitrectomy for prevention of macular holes— Results of a randomized multicenter clinical trial. Ophthal- mology 1994;101:1055–1059. 2. Gass JD. Idiopathic senile macular hole: its early stages and pathogenesis. Arch Ophthalmol 1988;106:629 – 639. 3. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes: results of a pilot study. Arch Ophthalmol 1991;109: 654 – 659. 4. Kokame GT, de Bustros S. The Vitrectomy for Prevention of Macular Hole Study Group. Visual acuity as a prognostic indicator in stage I macular holes. Am J Ophthalmol 1995; 120:112–114. 5. Kim JW, Freeman WR, Azen SP, El-Haig W, Klein DJ, Bailey IL. The Vitrectomy for Macular Hole Study Group. Prospec- tive randomized trial of vitrectomy or observation for stage 2 macular holes. Am J Ophthalmol 1996;121:605– 614. Macular Dystrophy in a 9-year-old Boy With Fundus Albipunctatus Makoto Nakamura, MD, and Yozo Miyake, MD PURPOSE: To report a 9-year-old boy with fundus albi- punctatus and macular dystrophy. DESIGN: Observational case report. METHODS: A complete ophthalmic examination was per- formed. The 11-cis retinol dehydrogenase gene (RDH5) was examined by direct genomic sequencing. Accepted for publication Sep 22, 2001. From the Department of Ophthalmology, Nagoya University School of Medicine, 65-Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. Supported by Grants for Research Committee on Chorioretinal De- generations from The Ministry of Health and Welfare of Japan and Grant-in-Aid for Scientific Research (Dr. Miyake, A13307048, Dr. Nakamura, C12671703) from the Ministry of Education, Science, Sports and Culture, Japan. Reprint requests to Makoto Nakamura, MD, Department of Ophthal- mology, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan; Fax 81-52-744-2278; e-mail: [email protected] AMERICAN JOURNAL OF OPHTHALMOLOGY 278 FEBRUARY 2002

Macular dystrophy in a 9-year-old boy with fundus albipunctatus

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three months or less with focal central distortion noted onthe Amsler grid. All patients did not see a break in a thinslit beam placed across the lesion (negative Watzke-Allensign) on initial evaluation. Patients underwent a completeophthalmologic examination, best corrected Snellen visualacuity, fundus photographs, and fluorescein angiography.Exclusion factors included high myopia over �6.5 diopt-ers, myopic macular degeneration, diabetic retinopathy, orage related macular degeneration. Most stage I holes wereinitially observed, but then managed in three groups: (I)observation only, if spontaneous resolution developed �7eyes; (II) pars plana vitrectomy, posterior cortical vitreousseparation, and fluid �20% sulfur hexafluoride gas ex-change if vision worsened to 20/50 or worse with a stage Ihole configuration �9 eyes; (III) pars plana vitrectomy,posterior cortical vitreous peeling, membrane peelingwithout internal limiting membrane peeling, fluid �18%perfluoropropane gas exchange for acute full-thicknesshole (stage II or III) �9 eyes. All patients had at least sixmonths and up to nine years of follow-up.

During observation (group I) spontaneous resolutiondeveloped in 7 eyes with all maintaining 20/40 or bettervision. Presenting vision in group I was 20/40 or better in5 eyes. Two patients with presenting vision of 20/60 to20/70 elected to observe and spontaneously resolved.Spontaneously resolved holes often showed a focal fovealfacet, similar to postoperative cases. In group II followingvitrectomy and fluid-gas exchange with sulfur hexafluoride,8 of 9 eyes did not progress and recovered 20/40 or bettervision (Figure 1, right). One of 9 eyes required a subse-quent surgery with perfluoropropane after macular holeprogression, but recovered 20/40 vision with hole closure.In 9 eyes which acutely progressed from stage I to afull-thickness hole (group III), pars plana vitrectomy,posterior cortical vitreous separation, membrane peeling,and fluid-gas exchange with perfluoropropane resulted inhole closure in all eyes, and recovery of 20/40 or bettervision. Of the 9 eyes in group II, one was previouslypseudophakic, two developed moderate cataracts, and sixunderwent cataract surgery. Of the 9 eyes in group III, twowere previously pseudophakic, one had a mild cataract,and six underwent cataract surgery. One of 18 operatedeyes (5%), an eye in group II, developed retinal detach-ment with reopening of the macular hole, but recovered20/20 vision with surgical repair.

Resolution of macular hole in the acute stages ofdevelopment allowed excellent anatomic and visual resultsin all three groups. All 25 patients recovered 20/40 orbetter vision at last follow-up. Stage I holes with poorvision (group II) progressed in 12% (1/9 eyes) followingvitrectomy with gas tamponade, which compares favorablywith the natural history of stage I macular holes withvision of 20/50 or worse (66% progression rate).4 This alsocompares favorably with the vitrectomy group in theVitrectomy for Prevention of Macular Hole Study (37%progression rate),1 which did not include intraocular gas

tamponade and whose progression rate may have beeneven higher if limited to high risk eyes with poor vision.4However, this present study is a retrospective and nonran-domized study with small numbers in each group. Inaddition, the risks of post-vitrectomy cataract formationand occasional retinal detachment must be weighedagainst the potential benefit of better vision potential withearlier intervention. Observation was recommended ini-tially in most cases, and is especially recommended forstage I holes with best corrected visual acuity of 20/40 orbetter due to the low progression rate.4 A randomizedclinical trial studying vitrectomy with intraocular gastamponade in stage I holes with poor vision versus inter-vention only after full-thickness hole development isindicated and may be aided by the use of optical coherencetomography for patient selection.

REFERENCES

1. De Bustros S. The Vitrectomy for Prevention of Macular HoleStudy Group. Vitrectomy for prevention of macular holes—Results of a randomized multicenter clinical trial. Ophthal-mology 1994;101:1055–1059.

2. Gass JD. Idiopathic senile macular hole: its early stages andpathogenesis. Arch Ophthalmol 1988;106:629–639.

3. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macularholes: results of a pilot study. Arch Ophthalmol 1991;109:654–659.

4. Kokame GT, de Bustros S. The Vitrectomy for Prevention ofMacular Hole Study Group. Visual acuity as a prognosticindicator in stage I macular holes. Am J Ophthalmol 1995;120:112–114.

5. Kim JW, Freeman WR, Azen SP, El-Haig W, Klein DJ, BaileyIL. The Vitrectomy for Macular Hole Study Group. Prospec-tive randomized trial of vitrectomy or observation for stage 2macular holes. Am J Ophthalmol 1996;121:605–614.

Macular Dystrophy in a 9-year-oldBoy With Fundus AlbipunctatusMakoto Nakamura, MD, and Yozo Miyake, MD

PURPOSE: To report a 9-year-old boy with fundus albi-punctatus and macular dystrophy.DESIGN: Observational case report.METHODS: A complete ophthalmic examination was per-formed. The 11-cis retinol dehydrogenase gene (RDH5)was examined by direct genomic sequencing.

Accepted for publication Sep 22, 2001.From the Department of Ophthalmology, Nagoya University School of

Medicine, 65-Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan.Supported by Grants for Research Committee on Chorioretinal De-

generations from The Ministry of Health and Welfare of Japan andGrant-in-Aid for Scientific Research (Dr. Miyake, A13307048, Dr.Nakamura, C12671703) from the Ministry of Education, Science, Sportsand Culture, Japan.

Reprint requests to Makoto Nakamura, MD, Department of Ophthal-mology, Nagoya University School of Medicine, 65 Tsuruma-cho,Showa-ku, Nagoya 466-8550, Japan; Fax �81-52-744-2278; e-mail:[email protected]

AMERICAN JOURNAL OF OPHTHALMOLOGY278 FEBRUARY 2002

RESULTS: The fundi of the 9-year-old boy showed nu-merous yellow-white punctata as well as foveal atrophiclesions in both eyes. His corrected visual acuity was RE:0.5 and LE: 0.3. Scotopic full-field electroretinogramswere not present after 20 minutes of dark-adaptation butwere normal after 3 hours of dark-adaptation. Full-fieldcone and 30-Hz flicker electroretinograms were normal;however, focal macular cone electroretinograms weresignificantly reduced. A compound heterozygous muta-tion of Tyr281His and Leu310GluVal in RDH5 wasdetected.CONCLUSION: We suggest that the macular dystrophy iscaused by the RDH5 mutation as a phenotype variation

in fundus albipunctatus. (Am J Ophthalmol 2002;133:278–280. © 2002 by Elsevier Science Inc. Allrights reserved.)

FUNDUS ALBIPUNCTATUS IS A TYPE OF CONGENITAL

night blindness with an autosomal recessive inheri-tance.1 Many discrete, small, round or elliptical, yellow-white lesions are seen throughout the fundus usuallyexcluding the macula.1 Normal scotopic and photopicelectroretinograms are recorded, but a long dark-adapta-tion period is necessary.1 The 11-cis retinol dehydrogenasegene (RDH5) was identified as the mutated gene in fundusalbipunctatus.2

FIGURE 1. Fundus photographs and fluorescein angiogram of the patient with fundus albipunctatus. (A) The left eye showsmultiple yellow-white lesions excluding the macula and an atrophic retinal lesion in the fovea. Insert shows a high magnification ofthe fovea. (B) Fluorescein angiography of the left eye shows no abnormality in the fovea.

FIGURE 2. (A) Full-field electroretinograms of a normal subject and this case. No scotopic electroretinogram and a “negative-shaped” bright-flash electroretinogram were recorded from our case after 20 minutes of dark adaptation (upper). Theelectroretinograms became normal after 3 hours of dark adaptation (lower). Photopic electroretinograms are normal. The arrowsindicate the stimulus onset. (B) Focal macular cone electroretinograms recorded from 5 degrees, 10 degrees, and 15 degrees of themacular area in a normal subject and our case. The amplitudes in our case are significantly reduced.

BRIEF REPORTSVOL. 133, NO. 2 279

We have shown that cone dystrophy frequently accom-panies fundus albipunctatus in elderly patients with RDH5mutations.3 In such cases, full-field photopic electroretino-grams are severely reduced, a bull’s-eye maculopathy ispresent, and visual acuity and fields are impaired.3,4 Weconcluded that mutations of the RDH5 lead to a progres-sive cone dystrophy resulting in severe loss of visualfunction with aging.3

To date, no fundus albipunctatus case with a maculopa-thy has been reported in a child. We describe a 9-year-oldJapanese boy who presented with a 2-year history of nightblindness with no family history of retinal diseases. Mul-tiple discrete yellow-white dots were observed at the levelof retinal pigment epithelium with scarring of the macula,in both eyes (Figure 1A). The eyes were otherwise normal.

Full-field electroretinograms elicited by Ganzfeld stimuliafter 20 minutes of dark adaptation showed no scotopicelectroretinograms and “negative-shaped” bright-flash elec-troretinograms. Normal scotopic b-wave and bright-flashelectroretinograms were recorded after 3 hours of dark adap-tation. Photopic electroretinograms were normal (Figure 2A).

Molecular genetic examination revealed a compoundheterozygous mutation, a T to C mutation at nucleotide841 (Tyr281His), and a C deletion at nucleotide 928 withinsertion of GAAG (Leu310GluVal) in RDH5. His nor-mal father showed a heterozygous mutation at nucleotide841 and was normal at nucleotide 928. No such basesubstitutions were recognized in 100 alleles from normalindividuals.

Unexpectedly for a young patient with fundus albipunc-tatus,3 his fundi demonstrated symmetric atrophic lesionsin the macula in both eyes (Figure 1A), and his correctedvisual acuity was RE: 0.5 and LE: 0.3. Fluorescein angiog-raphy was normal in the macula (Figure 1B). Focal conemacular electroretinograms5 (time constant, 0.03 seconds)demonstrated that the a- and b-waves were absent from 5degrees and 10 degrees, and significantly reduced for 15° ofthe macula (Figure 2B). Because the function of his retinawas deteriorated especially in the macula, he was found tohave macular dystrophy and fundus albipunctatus.

This case is different from previously reported elderlypatients3 because the patient did not show a bull’s eye buta foveal atrophy. He was not affected by general conedystrophy because the full-field photopic electroretino-grams were normal. We cannot determine whether themacular dystrophy is caused by a phenotypic variation offundus albipunctatus or by a chance combination withfundus albipunctatus, however, we suggest that the macu-lar dystrophy is caused by RDH5 mutation because manyelderly patients with RDH5 mutations develop maculopa-thy.3 Although the two mutations of Tyr281His andLeu310GluVal have been reported in other Japanese casesof fundus albipunctatus,3 no case with this combination ofa compound heterozygous mutation has been reported. It isnot clear whether the phenotype in this case resulted fromthe genotype, and further data will be necessary to under-

stand the clinical features and the genotype–phenotypecorrelation with the RDH5 mutations.

ACKNOWLEDGMENTThe authors would like to thank Masakazu Nagase fortechnical assistance in the analysis of RDH5.

REFERENCES

1. Heckenlively J. Congenital stationary night blindness. Geneticdiseases of the eye. New York: Oxford University Press; 1998:389–396.

2. Yamamoto H, Simon A, Eriksson U, et al. Mutations in the geneencoding 11-cis retinol dehydrogenase cause delayed dark adap-tation and fundus albipunctatus. Nat Genet 1999;22:188–191.

3. Nakamura M, Hotta Y, Tanikawa A, Terasaki H, Miyake Y. Ahigh association with cone dystrophy in fundus albipunctatuscaused by mutations of the RDH5 gene. Invest OphthalmolVis Sci 2000;41:3925–3932.

4. Miyake Y, Shiroyama N, Sugita S, Horiguchi M, Yagasaki K.Fundus albipunctatus associated with cone dystrophy. Br JOphthalmol 1992;76:375–379.

5. Miyake Y, Shiroyama I, Ota I, Horiguchi M. Oscillatorypotentials in electroretinograms of the human macular region.Invest Ophthalmol Vis Sci 1988;29:1631–1635.

Spontaneous Reopening of aSpontaneously Closed Macular HoleGregg T. Kokame, MD, andMatthew B. McCauley, MD

PURPOSE: To report a case of spontaneous reopening afterspontaneous closure of a full-thickness macular hole.METHODS: Observational case report. Retrospective clin-ical practice case review.RESULTS: A 57-year-old man with a full-thickness mac-ular hole in his left eye developed spontaneous closurefor 1.5 years with improved vision, followed by sponta-neous reopening of the hole with loss of vision. Surgicalrepair resulted in repeat closure and recovery of 20/20visual acuity.CONCLUSION: Spontaneous reopening, which occasion-ally occurs after surgical closure of macular holes, canalso occur after spontaneous closure of a macular hole.(Am J Ophthalmol 2002;133:280–282. © 2002 byElsevier Science Inc. All rights reserved.)

Accepted for publication Sep 19, 2001.From the Division of Ophthalmology, Department of Surgery, Univer-

sity of Hawaii School of Medicine, Honolulu, Hawaii (G.T.K.), TheRetina Center at Pali Momi, Kapi’olani Health, Aiea, Hawaii (G.T.K.),and Tripler Army Medical Center, Honolulu, Hawaii (M.B.M.).

Presented at the Biannual meeting of the Western Association forVitreoretinal Education Meeting, Wailea, Maui, Hawaii, July 3, 2001.

Inquiries to Gregg T. Kokame, MD, Medical Director, The RetinaCenter at Pali Momi, 98-1079 Moanalua Rd, Suite 470, Aiea, Hawaii96701; fax (808) 487-3699; e-mail: [email protected]

AMERICAN JOURNAL OF OPHTHALMOLOGY280 FEBRUARY 2002