may reduce the need for retreatments caused by persistence orrecurrences of the choroidal neovascularization.

In conclusion, our data clearly show that the rate ofidentification of the feeder vessel remains low, even usingdynamic indocyanine green angiography, in eyes with un-treated classic subfoveal choroidal neovascularization, limit-ing a diffuse application of feeder vessel treatment as aprimary procedure in these eyes. However, the feeder vesseldetection rate significantly increases after photodynamictherapy, allowing a different therapeutic approach to persis-tent or recurrent choroidal neovascularization, instead ofrepeating photodynamic therapy. Large trials are necessary tovalidate the long-term efficacy of this multimodality approachin the treatment of subfoveal choroidal neovascularization.

REFERENCES

1. Bressler NM. Treatment of Age-Related Macular Degenera-tion with Photodynamic Therapy (TAP) Study Group. Pho-todynamic therapy of subfoveal choroidal neovascularizationin age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2. ArchOphthalmol 2001;119:198–207.

2. Shiraga F, Ojima Y, Matsuo T, Takasu I, Matsuo N. Feedervessel photocoagulation of subfoveal choroidal neovascular-ization secondary to age-related macular degeneration. Oph-thalmology 1998;105:662–669.

3. Staurenghi G, Orzalesi N, La Capria A, Aschero M. Lasertreatment of feeder vessels in subfoveal choroidal neovascularmembranes. Ophthalmology 1998;105:2297–2305.

4. Flower R. Experimental studies of indocyanine green dye-enhanced photocoagulation of choroidal neovascularizationfeeder vessels. Am J Ophthalmol 2000;129:501–512.

5. Reichel E, Berrocal AM, Ip M, et al. Transpupillary thermo-therapy of occult subfoveal choroidal neovascularization inpatients with age-related macular degeneration. Ophthalmol-ogy 1999;106:1908–1914.

6. Verteporfin in Photodynamic Therapy Study Group. Verte-porfin therapy of subfoveal choroidal neovascularization inage-related macular degeneration: two-year results of a ran-domized clinical trial including lesions with occult with noclassic choroidal neovascularization–verteporfin in photody-namic therapy report 2. Am J Ophthalmol 2001;131:541–560.

7. Flower RW, von Kerczek C, Zhu L, et al. Theoreticalinvestigation of the role of choriocapillaris blood flow intreatment of subfoveal choroidal neovascularization associatedwith age-related macular degeneration. Am J Ophthalmol2001;132:85–93.

Enhanced S-cone Syndrome WithSubfoveal NeovascularizationMakoto Nakamura, MD, Yoshihiro Hotta, MD,Chang-Hua Piao, MD, Mineo Kondo, MD,Hiroko Terasaki, MD, and Yozo Miyake, MD

PURPOSE: To report a case of enhanced S-cone syndromeassociated with subfoveal neovascularization.DESIGN: Observational case report.METHODS: A 23-year-old man, who was first examined atage 9 years, was found to have enhanced S-cone syn-

drome by clinical, electrophysiological, and moleculargenetic examinations.RESULTS: At 9 years of age, a subfoveal neovasculariza-tion was present in his right eye and corrected visualacuity was RE: 0.15 and LE: 1.0. After he was 20 yearsold, cystoid changes in the macula of the left eye appearedand visual acuity, in the left eye, decreased from 1.0 to0.02.CONCLUSION: The clinical course of enhanced S-conesyndrome is progressive, and we suggest that the subreti-nal neovascularization is a phenotypic variation of en-hanced S-cone syndrome. (Am J Ophthalmol 2002;133:575–577. © 2002 by Elsevier Science Inc. Allrights reserved.)

THE ENHANCED S-CONE SYNDROME IS A NIGHT BLIND-

ness syndrome with an autosomal recessive hereditarypattern.1,2 The maculae are abnormal and often showcystoid changes. Also, pigmentary changes occur in theregion of the vascular arcades. This syndrome was namedthe enhanced S-cone syndrome because the cone electro-retinogram to short wavelength stimuli is enhanced,whereas the cone electroretinograms to long and middlewavelength stimuli are significantly reduced. The rodelectroretinogram is nonrecordable.1,2

The NR2E3 gene, which encodes a ligand-dependenttranscription factor and is considered to determine photo-receptor fate during development, was identified as themutated gene in patients with the enhanced S-conesyndrome.3

Although it was reported that one enhanced S-conesyndrome patient developed a subretinal neovasculariza-tion unilaterally, a detailed description of this case was notpresented.1 We report a Japanese enhanced S-cone syn-drome case that demonstrated a subfoveal neovasculariza-tion in one eye and cystoid changes in the macula of theother eye during a 14-year follow-up.

The case first presented at 9 years of age because of nightblindness in both eyes and poor corrected visual acuity inthe right eye. His best-corrected visual acuity was RE: 0.15and LE: 1.0. A subretinal hemorrhage was noted in theright macula, and fluorescein angiography demonstratedhyperfluorescence that became stronger with time, whichindicated the presence of a subretinal neovascularization

Accepted for publication Dec 7, 2001.From the Department of Ophthalmology, Nagoya University School of

Medicine, Showa-ku, Nagoya, Japan.Supported by a Grant-in-Aid for Scientific Research (Y.M.,

A13307048; M.N., C12671703) from the Ministry of Education, Science,Sports and Culture, Japan.

Inquiries to Makoto Nakamura, MD, Department of Ophthalmology,Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku,Nagoya 466-8550, Japan; fax: (�81) 52-744-2278; e-mail: makonaka@med.nagoya-u.ac.jp

BRIEF REPORTSVOL. 133, NO. 4 575

(Figure 1). A macular pigment epithelial abnormality wasobserved in the left eye. He had no sign or history ofrubella, although most macular neovascularizations inyoung Japanese patients are caused by it. Serum examina-tion did not suggest any infection, including toxoplasmosisor syphilis. Although an unusual large, slow waveform wasrecorded with a portable 20-J bright-flash electroretino-gram, the concept of enhanced S-cone syndrome was notknown at that time.

The subretinal hemorrhage and neovascular membranein the right eye persisted during the follow-up (Figure 2),and the visual acuity in the right eye fluctuated between0.03 and 0.3, and it was 0.2 on his last visit. Cystoidchanges in the left macula were first noted when he was 20years old and subsequently enlarged. The visual acuity inthe left eye was reduced to 0.02 and was uncorrectable at23 years of age. The macular pigment epithelial abnormal-ity in the left eye did not change during the follow-up(Figure 2). Diffuse pigmentary changes within the vasculararcades appeared and gradually became prominent in both(Figure 2).

Electrophysiological examination showed no scotopicresponses and a large b-wave with a prolonged implicittime in the rod-cone mixed electroretinogram. The ampli-tude of the blue cone electroretinogram was markedlylarger than normal, and the red cone electroretinogramwas significantly reduced.

The NR2E3 gene was analyzed by direct genomicsequencing after informed consent, and a homozygousmutation of Arg311Glu (CGG to CAG) in exon 6 wasidentified. His unaffected consanguineous parents wereheterozygous for the mutation. The same mutation hasbeen found in 13 out of 35 enhanced S-cone syndrome

families abroad,3 which indicates a hot spot for thedisorder.

Although the clinical features of enhanced S-conesyndrome have not been fully described, it has beensuggested that enhanced S-cone syndrome may be aprogressive disease because the visual acuity in somepatients decreases and the degenerative changes in thearcade region become more prominent during follow-up.1

The clinical course in our case with the appearance ofcystoid changes and the reduction of visual acuity supportsthe progressive nature. The subretinal neovascularizationis most likely a phenotypic occurrence in the enhancedS-cone syndrome, and a young patient with macularneovascularization and night blindness should be consid-ered to be possibly affected by enhanced S-cone syndrome.

ACKNOWLEDGMENTS

The authors thank Masakazu Nagase for technical assis-tance in the analysis of NR2E3.

REFERENCES

1. Marmor MF, Jacobson SG, Foerster MH, Kellner U, WeleberRG. Diagnostic clinical findings of a new syndrome with nightblindness, maculopathy, and enhanced S cone sensitivity.Am J Ophthalmol 1990;110:124–134.

2. Jacobson SG, Marmor MF, Kemp CM, Knighton RW. SWS(blue) cone hypersensitivity in a newly identified retinaldegeneration. Invest Ophthalmol Vis Sci 1990;31:827–838.

3. Haider NB, Jacobson SG, Cideciyan AV, et al. Mutation of anuclear receptor gene, NR2E3, causes enhanced S conesyndrome, a disorder of retinal cell fate. Nat Genet 2000;24:127–131.

FIGURE 1. Fundus photographs and fluorescein angiogram of the patient with enhanced S-cone syndrome taken when he was 9years old. (Left) The right eye shows a subretinal hemorrhage in the macula. (Right) Fluorescein angiogram of the right eye showshyperfluorescence corresponding to the neovascular membrane.

AMERICAN JOURNAL OF OPHTHALMOLOGY576 APRIL 2002

FIGURE 2. Fundus photographs and fluorescein angiograms of the patient with enhanced S-cone syndrome taken when he was 23years old. (Top left) The right eye shows a persistent subretinal hemorrhage and an area of hypopigmentation in the macula.Pigmentary changes are present in the vascular arcade region. (Middle left) An early fluorescein angiogram of the right eye showsdiffuse hyperfluorescence that corresponds to an area of hypopigmentation at the level of the retinal pigment epithelium in themacula. (Bottom left) A late fluorescein angiogram of the right eye shows an appearance of an inverted C-shaped hyperfluorescentarea in the macula, which indicates the persistence of the neovascular membrane. (Top right) The left eye shows cystoid-likechanges and pigment epithelial abnormality in the macula as well as the diffuse pigmentary changes in the vascular arcade region.(Middle right) Fluorescein angiogram of the left eye shows hyperfluorescence corresponding to the pigment epithelial abnormalityin the macula.

BRIEF REPORTSVOL. 133, NO. 4 577