LATE-ONSET RETINAL MACULAR DEGENERATION: AN ENTITY NOT TO BE OVERLOOKED Anita Agarwal, MD,* Janice C. Law, MD,* Ryan M. Tarantola, MD†
Purpose: To describe a patient with extensive geographic atrophy and night blindness. Methods: A 59-year-old Caucasian woman of German descent presenting with progressive visual difficulty in the dark for 5 years was examined. Results: Her visual acuity was 20/400 in the right eye and 20/50 in the left eye. Fundus examination of both eyes showed multiple islands of geographic atrophy involving most of the posterior pole and temporal retina. There were yellow drusen-like flecks in the nasal retina. The fluorescein angiogram showed window defects and the corresponding atrophic areas showed decreased autofluorescence. A Goldmann visual field showed central scotoma and marked constriction on the right and moderate constriction on the left. An electroretinogram showed markedly decreased rod and cone function in both eyes. Conclusion: Late-onset retinal macular degeneration is a rare degenerative condition that should not be mistaken for age-related macular degeneration. RETINAL CASES & BRIEF REPORTS 4:257–261, 2010
correction was right eye 27.50 + 2.00 3 10 and left eye 24.50 + 1.00 3 155. She was otherwise healthy. Her father was adopted and was known to have poor vision late in his life. She has a younger brother and sister who are asymptomatic and live in Germany. She has two sons aged 32 and 34 years who so far have no visual deficits. Her best-corrected visual acuity was 20/400 in the right eye and 20/50 in the left eye. Anterior segment examination was normal in both eyes. Fundus examination of both eyes showed multiple islands of geographic atrophy involving most of the posterior pole and temporal retina (Figure 1). There were yellow drusen-like flecks in the nasal retina without islands of atrophy (Figure 1, C). The fluorescein angiogram showed window defects and the corresponding atrophic areas showed decreased autofluorescence (Figure 2). A Goldmann visual field showed central scotoma and marked constriction on the right and moderate constriction on the left (Figure 3). An electroretinogram showed markedly decreased rod and cone function in both eyes. Amino acid testing revealed an ornithine level of 102 (normal range, 48–195), glutamine 652 (normal range, 206–756), glutamic acid 35 (normal range, 10–131), glycine 186 (normal range, 151–490), citrilline 46 (normal range, 12–55), and arginine 53 (normal range, 15–128) mmol/L, all within the normal range, thus ruling out gyrate atrophy.
From *Vanderbilt Eye Institute, Nashville, Tennessee; and †Department of Ophthalmology, University of Iowa, Iowa City, Iowa.
G
eographic atrophy is a feature commonly seen in age-related macular degeneration and in less common entities such as Sorsby macular dystrophy, gyrate atrophy, and central choroidal areolar atrophy. A rare but definite entity, late-onset retinal macular degeneration is described to bring awareness of this condition lest it be mistakenly diagnosed as agerelated macular degeneration.
Case Report A 59-year-old Caucasian woman of German descent presented with progressive visual difficulty in the dark for 5 years. The right eye was amblyopic secondary to anisometropia. Her refractive
Comment Late-onset retinal macular degeneration is an autosomal-dominant condition that presents in midlife with night vision problems and progresses rapidly to significant visual impairment.
The authors have no conflicts of interest to disclose. Reprint requests: Anita Agarwal, MD, Section of Vitreoretinal Surgery, Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232-8808; e-mail: [email protected]
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Fig. 1. Fundus photograph of the posterior pole of the right eye and left eye showing islands of retinal pigment epithelium atrophy with scalloped margins sparing the center of the fovea (A and B). Nasal retina of the left eye showing yellow drusen-like flecks (C, arrow). Similar lesions in the temporal periphery and sparing of nasal periphery in both eyes (D and E).
C O L O R
The earliest manifestation is delayed dark adaptation in the fifth or sixth decade that progresses to night blindness.1,2 The typical fundus changes also appear in midlife; the patients have yellow deposits akin to drusen early in the disease.3 (Figure 1, C, arrow). After this, islands of geographic atrophy develop when these patients are mistakenly diagnosed as having agerelated macular degeneration. This case illustrates the typical appearance of the atrophy with scallopedshaped intervening retina. Histopathologically, there is deposition of extracellular lipid and protein between the retinal pigment epithelium and Bruch membrane. Loss of overlying photoreceptors and thinning of the retinal pigment epithelium ensue, resulting in loss of rod and cone function. Our patient did not show bone spicule pigment change; however, this can occur over time from photoreceptor death. These patients can also develop choroidal neovascular membranes similar to
age-related macular degeneration and Sorsby fundus dystrophy. Three patients with abnormally long lens zonules have been described,4 although this was not seen in our patient. The two living asymptomatic siblings of the patient reside outside the country and could not be examined. Her sons are 32 and 34 years of age and have been advised to undergo ophthalmic evaluation. In approximately half of the cases, the autosomal-dominant inheritance is the result of a single founder mutation in the C1QTNF5 (formerly called CTRP5) gene.4–6 In other families, the disease locus is unlinked to this region and the gene(s) remain to be identified.
Key words: LORMD, late-onset retinal macular degeneration, geographic atrophy, sub-Bruch membrane deposits, rod–cone degeneration.
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Fig. 2. Fluorescein angiogram showing window defect corresponding to the atrophic lesions (A and B). Decreased autofluorescence of the atrophic lesions in both eyes (C and D).
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Fig. 3. Constricted visual fields worse in the right eye than left; the right eye has amblyopia in addition (A and B).
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Fig. 3. (Continued).
References 1. Kuntz CA, Jacobson SG, Cideciyian AV, et al. Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration. Invest Ophthalmol Vis Sci 1996;37:1772–1782. 2. Jacobson SG, Cideciyan AV, Wright E, Wright AF. Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. Invest Ophthalmol Vis Sci 2001;42:1882–1890. 3. Milam AH, Curcio CA, Cideciyan AV, et al. Dominant lateonset retinal degeneration with regional variation of sub-retinal pigment epithelium deposits, retinal function, and photoreceptor degeneration. Ophthalmology 2000;107:2256–2266.
4. Subrayan V, Morris B, Armbrecht AM, Wright AF, Dhillon B. Long anterior lens zonules in late-onset retinal degeneration (L-ORD). Am J Ophthalmol 2005;140:1127–1129. 5. Hayward C, Shu X, Cideciyan AV, et al. Mutation in a shortchain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration. Hum Mol Genet 2003;12: 2657–2667. 6. Ayyagari R, Mandal NA, Karoukis AJ, et al. Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest Ophthalmol Vis Sci 2005;46: 3363–3371.
Purpose: To describe a patient with extensive geographic atrophy and night blindness. Methods: A 59-year-old Caucasian woman of German descent presenting with progressive visual difficulty in the dark for 5 years was examined. Results: Her visual acuity was 20/400 in the right eye and 20/50 in the left eye. Fundus examination of both eyes showed multiple islands of geographic atrophy involving most of the posterior pole and temporal retina. There were yellow drusen-like flecks in the nasal retina. The fluorescein angiogram showed window defects and the corresponding atrophic areas showed decreased autofluorescence. A Goldmann visual field showed central scotoma and marked constriction on the right and moderate constriction on the left. An electroretinogram showed markedly decreased rod and cone function in both eyes. Conclusion: Late-onset retinal macular degeneration is a rare degenerative condition that should not be mistaken for age-related macular degeneration. RETINAL CASES & BRIEF REPORTS 4:257–261, 2010
correction was right eye 27.50 + 2.00 3 10 and left eye 24.50 + 1.00 3 155. She was otherwise healthy. Her father was adopted and was known to have poor vision late in his life. She has a younger brother and sister who are asymptomatic and live in Germany. She has two sons aged 32 and 34 years who so far have no visual deficits. Her best-corrected visual acuity was 20/400 in the right eye and 20/50 in the left eye. Anterior segment examination was normal in both eyes. Fundus examination of both eyes showed multiple islands of geographic atrophy involving most of the posterior pole and temporal retina (Figure 1). There were yellow drusen-like flecks in the nasal retina without islands of atrophy (Figure 1, C). The fluorescein angiogram showed window defects and the corresponding atrophic areas showed decreased autofluorescence (Figure 2). A Goldmann visual field showed central scotoma and marked constriction on the right and moderate constriction on the left (Figure 3). An electroretinogram showed markedly decreased rod and cone function in both eyes. Amino acid testing revealed an ornithine level of 102 (normal range, 48–195), glutamine 652 (normal range, 206–756), glutamic acid 35 (normal range, 10–131), glycine 186 (normal range, 151–490), citrilline 46 (normal range, 12–55), and arginine 53 (normal range, 15–128) mmol/L, all within the normal range, thus ruling out gyrate atrophy.
From *Vanderbilt Eye Institute, Nashville, Tennessee; and †Department of Ophthalmology, University of Iowa, Iowa City, Iowa.
G
eographic atrophy is a feature commonly seen in age-related macular degeneration and in less common entities such as Sorsby macular dystrophy, gyrate atrophy, and central choroidal areolar atrophy. A rare but definite entity, late-onset retinal macular degeneration is described to bring awareness of this condition lest it be mistakenly diagnosed as agerelated macular degeneration.
Case Report A 59-year-old Caucasian woman of German descent presented with progressive visual difficulty in the dark for 5 years. The right eye was amblyopic secondary to anisometropia. Her refractive
Comment Late-onset retinal macular degeneration is an autosomal-dominant condition that presents in midlife with night vision problems and progresses rapidly to significant visual impairment.
The authors have no conflicts of interest to disclose. Reprint requests: Anita Agarwal, MD, Section of Vitreoretinal Surgery, Vanderbilt Eye Institute, 2311 Pierce Avenue, Nashville, TN 37232-8808; e-mail: [email protected]
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Fig. 1. Fundus photograph of the posterior pole of the right eye and left eye showing islands of retinal pigment epithelium atrophy with scalloped margins sparing the center of the fovea (A and B). Nasal retina of the left eye showing yellow drusen-like flecks (C, arrow). Similar lesions in the temporal periphery and sparing of nasal periphery in both eyes (D and E).
C O L O R
The earliest manifestation is delayed dark adaptation in the fifth or sixth decade that progresses to night blindness.1,2 The typical fundus changes also appear in midlife; the patients have yellow deposits akin to drusen early in the disease.3 (Figure 1, C, arrow). After this, islands of geographic atrophy develop when these patients are mistakenly diagnosed as having agerelated macular degeneration. This case illustrates the typical appearance of the atrophy with scallopedshaped intervening retina. Histopathologically, there is deposition of extracellular lipid and protein between the retinal pigment epithelium and Bruch membrane. Loss of overlying photoreceptors and thinning of the retinal pigment epithelium ensue, resulting in loss of rod and cone function. Our patient did not show bone spicule pigment change; however, this can occur over time from photoreceptor death. These patients can also develop choroidal neovascular membranes similar to
age-related macular degeneration and Sorsby fundus dystrophy. Three patients with abnormally long lens zonules have been described,4 although this was not seen in our patient. The two living asymptomatic siblings of the patient reside outside the country and could not be examined. Her sons are 32 and 34 years of age and have been advised to undergo ophthalmic evaluation. In approximately half of the cases, the autosomal-dominant inheritance is the result of a single founder mutation in the C1QTNF5 (formerly called CTRP5) gene.4–6 In other families, the disease locus is unlinked to this region and the gene(s) remain to be identified.
Key words: LORMD, late-onset retinal macular degeneration, geographic atrophy, sub-Bruch membrane deposits, rod–cone degeneration.
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Fig. 2. Fluorescein angiogram showing window defect corresponding to the atrophic lesions (A and B). Decreased autofluorescence of the atrophic lesions in both eyes (C and D).
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Fig. 3. Constricted visual fields worse in the right eye than left; the right eye has amblyopia in addition (A and B).
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Fig. 3. (Continued).
References 1. Kuntz CA, Jacobson SG, Cideciyian AV, et al. Sub-retinal pigment epithelial deposits in a dominant late-onset retinal degeneration. Invest Ophthalmol Vis Sci 1996;37:1772–1782. 2. Jacobson SG, Cideciyan AV, Wright E, Wright AF. Phenotypic marker for early disease detection in dominant late-onset retinal degeneration. Invest Ophthalmol Vis Sci 2001;42:1882–1890. 3. Milam AH, Curcio CA, Cideciyan AV, et al. Dominant lateonset retinal degeneration with regional variation of sub-retinal pigment epithelium deposits, retinal function, and photoreceptor degeneration. Ophthalmology 2000;107:2256–2266.
4. Subrayan V, Morris B, Armbrecht AM, Wright AF, Dhillon B. Long anterior lens zonules in late-onset retinal degeneration (L-ORD). Am J Ophthalmol 2005;140:1127–1129. 5. Hayward C, Shu X, Cideciyan AV, et al. Mutation in a shortchain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration. Hum Mol Genet 2003;12: 2657–2667. 6. Ayyagari R, Mandal NA, Karoukis AJ, et al. Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation. Invest Ophthalmol Vis Sci 2005;46: 3363–3371.
