CLINICAL SCIENCES. Visual Acuity in 3422 Consecutive Eyes With Choroidal Nevus

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1 CLINICAL SCIENCES Visual Acuity in 3422 Consecutive Eyes With Choroidal Nevus Carol L. Shields, MD; Minoru Furuta, MD; Arman Mashayekhi, MD; Edwina L. Berman, MBBS; Jonathan D. Zahler, DO; Daniel M. Hoberman, BS; Diep H. Dinh, BS; Jerry A. Shields, MD Objective: To evaluate visual acuity in eyes with choroidal nevus. Design: This was an observational case series. Of 3422 consecutive eyes with choroidal nevus, vision loss at 15 years occurred in 2% of eyes with extrafoveolar nevus and in 26% of eyes with subfoveolar nevus, particularly those with overlying retinal pigment epithelial detachment and foveal edema. A retrospective medical record review was conducted, with evaluation of visual acuity at presentation and at final examination. The main outcome measure was visual acuity. Results: The median visual acuity at presentation was 20/20 for eyes with either extrafoveolar or subfoveolar choroidal nevus. Using Kaplan-Meier estimates, vision loss of 3 or more logarithm of the minimum angle of resolution (logmar) lines at 5, 10, and 15 years occurred in less than 1%, 1%, and 2% of eyes with extrafoveolar nevus compared with 15%, 20%, and 26% of eyes with subfoveolar choroidal nevus, respectively. By multivariate analysis, factors predictive of visual loss of 3 or more log- MAR lines included subfoveolar nevus location (relative risk [RR], 15.52), juxtapapillary nevus location (RR, 4.52), initial visual acuity of 20/50 (RR, 15.40), overlying retinal pigment epithelial detachment (RR, 22.16), and foveal edema (RR, 9.02). Factors predictive of poor final visual acuity of 20/200 included subfoveolar nevus location (RR, 11.32), overlying orange pigment (RR, 3.68), overlying retinal pigment epithelial detachment (RR, 12.80), and foveal edema (RR, 18.72). Conclusion: Mild vision loss over many years should be anticipated in patients with subfoveolar choroidal nevus, particularly those with overlying retinal pigment epithelial detachment, orange pigment, and foveal edema. Arch Ophthalmol. 2007;125(11): Author Affiliations: Ocular Oncology Service, Wills Eye Institute, Thomas Jefferson University, hiladelphia, ennsylvania. CHOROIDAL NEVUS IS THE most common clinically detected intraocular tumor. 1,2 In the Blue Mountains Eye Study, 3 choroidal nevi were found in 7% of the white population. This benign tumor manifests as a pigmented or nonpigmented mass deep to the retina, often with overlying drusen and retinal pigment epithelial (RE) alterations. 1-7 Choroidal nevus can produce central vision loss and peripheral visual field loss. 4,8-11 Rarely, choroidal nevus can evolve into malignant melanoma. 7,12-18 Visual field defects were documented in 38% of 42 eyes with choroidal nevus evaluated by Tamler and Maumenee 4 and in 85% of 21 eyes analyzed by Flindall and Drance 10 using static and kinetic techniques. In 1971, Naumann and associates 6 found central visual acuity loss in 13 of 124 eyes (10%) with choroidal nevus. Gonder and coworkers 8 later described 206 patients with choroidal nevi posterior to the equator of the eye and found 22 (11%) with visual acuity loss. The vision loss was because of subfoveal fluid (50%), presumed photoreceptor degeneration (42%), and choroidal neovascularization (8%). 8 In 2005, Shields and associates 11 evaluated optical coherence tomography (OCT) of the retina overlying 120 consecutive patients with choroidal nevus to better ascertain the reasons for visual loss and found overlying retinal edema (15%), photoreceptor attenuation (51%), retinal thinning (22%), subretinal fluid (26%), and RE detachment (12%). In this report, we analyze a large cohort of 3422 eyes with stable choroidal nevus to ascertain initial and final visual acuity, loss of visual acuity over time, and factors related to visual acuity outcomes. METHODS A retrospective medical record review was performed on all patients with the clinical 1501

2 Table 1. Choroidal Nevus in 3422 Eyes of 3187 atients: Comparison of Clinical Features at Initial Examination for Extrafoveolar vs Subfoveolar Nevus Location of Choroidal Nevus a Clinical Feature Extrafoveolar Subfoveolar Age, y (n=3187) b 60 (62±15) [4-97] 58 (60±18) [4-93] Race (n=3187) White 2945 (98.5) 196 (99.0) African American 21 (0.7) 0 Hispanic 16 (0.5) 2 (1.0) Asian 6 (0.2) 0 Asian Indian 1 (0.03) 0 Sex (n=3187) Male 1095 (36.6) 75 (37.9) Female 1894 (63.4) 123 (62.1) Symptoms (n=3422) Decreased vision 160 (5.0) 62 (30.2) Visual field defect 33 (1.0) 5 (2.4) hotopsia or floaters 140 (4.4) 11 (5.4) None 2884 (89.6) 127 (62.0) Snellen visual acuity (logmar) (n=3422) 20/20-20/40 (0-0.3) 2984 (92.8) 154 (75.1) 20/50-20/100 ( ) 178 (5.5) 39 (19.0) 20/200 ( 1.0) 55 (1.7) 12 (5.9) Tumor base, mm (n=3422) b 5.1 (5.0±2.8) [ ] 5.7 (4.5±3.8) [ ] Tumor thickness, mm (n=3422) b 1.6 (1.5±0.5) [ ] 1.7 (1.6±0.5) [ ] Tumor color (n=3422) igmented 2460 (76.5) 169 (82.4) Nonpigmented 347 (10.8) 27 (13.2) Mixed 410 (12.7) 9 (4.4) Related retinal or RE findings (n=3422) Foveal edema 11 (0.3) 14 (6.8) Retinal invasion 5 (0.2) 1 (0.5) Subretinal fluid 285 (9.0) 60 (29.3) Subfoveal fluid 57 (1.8) 37 (18.0) Orange pigment 185 (5.8) 53 (25.9) RE hyperplasia 240 (7.6) 9 (4.4) RE detachment 33 (1.0) 9 (4.4) RE fibrous metaplasia 252 (7.9) 11 (5.4) RE atrophy 356 (11.2) 12 (5.9) Drusen 1735 (54.7) 84 (41.0) Choroidal neovascularization 13 (0.4) 7 (3.4) Abbreviations: logmar, logarithm of the minimum angle of resolution; RE, retinal pigment epithelium. a Data are given as number (percentage) of each group unless otherwise indicated. ercentages may not total 100 because of rounding. For the extrafoveolar group, n=2989 eyes for race and sex; n=3217 eyes for symptoms, Snellen visual acuity, and tumor color; and n=3172 eyes for related retinal/re findings. For the subfoveolar group, n=198 for race and sex; and n=205 for symptoms, Snellen visual acuity, tumor color, and related retinal/re findings. b Data are given as mean (median±sd) [range]. diagnosis of choroidal nevus evaluated at the Ocular Oncology Service at Wills Eye Institute between April 1, 1970, and June 1, Institutional review board approval was obtained for this retrospective study. atients with evidence of tumor transformation into melanoma were not included in the analysis. Clinical data were collected at initial examination regarding patient age, race, sex, medical history (dysplastic nevus syndrome; cutaneous, choroidal, or conjunctival melanoma; or neurofibromatosis), ocular melanocytosis, symptoms, and best-corrected visual acuity by Snellen charts. Vision data were evaluated using logarithm of the minimum angle of resolution (logmar) conversion. Data regarding specific features of the tumor were collected from large detailed fundus drawings that were made of each patient at first examination and from fundus photographs. These data included tumor epicenter quadrantic location (inferior, temporal, superior, nasal, or macular), tumor epicenter anteroposterior location (macular, macular to equator, or equator to ora serrata), distance of the tumor margin to the optic disc margin and foveola (in millimeters), largest tumor basal dimension and thickness (in millimeters), tumor color (pigmented, mixed, or nonpigmented), and presence of amelanotic halo around the nevus (halo nevus). Other related data included subretinal fluid, orange pigment, drusen, RE alterations (hyperplasia, detachment, fibrosis, and atrophy), and choroidal neovascular membrane. The status of the foveola (involvement with underlying choroidal nevus, subretinal fluid, and retinal edema) was recorded. The final best-corrected visual acuity at date last seen was recorded. A series of univariate Cox proportional hazards regressions assessed the degree of relationship of all of the variables previously listed to 3 outcomes, including the initial visual acuity, final visual acuity, and visual acuity loss of 3 or more logmar lines. All of the variables were analyzed as discrete variables except for patient age at presentation, tumor basal dimension, tumor thickness, and distance of the tumor to the optic disc 1502

3 A B Figure 1. Clinical appearance of pigmented extrafoveolar (A) vs pigmented subfoveolar (B) nevus in eyes without overlying retinal or retinal pigment epithelial changes (the visual acuity was 20/20 in both eyes). margin and foveola, which were evaluated as continuous variables. Subsequent multivariate models included variables that were significant on a univariate level (.05) to identify the combination of factors best related to the 3 outcomes. Kaplan- Meier survival estimates were calculated on time to loss of 3 or more lines of logmar visual acuity. RESULTS There were 3422 eyes of 3187 patients with choroidal nevus. The mean patient age at presentation was 60 years (median, 62 years; range, 4-97 years). The patient and tumor features are listed in Table 1. The tumor was subfoveolar in 205 (6.0%) eyes and extrafoveolar in 3217 (94.0%) eyes. The mean tumor base and thickness was 5.7 and 1.7 mm for the subfoveolar nevi, respectively, and 5.1 and 1.6 mm for the extrafoveolar nevi, respectively. Eyes with subfoveolar nevus displayed subretinal fluid in 60 cases and foveal retinal edema in 14 cases, compared with 285 cases and 11 cases, respectively, in eyes with extrafoveolar nevus (Table 1). The mean initial logmar visual acuity for extrafoveolar and subfoveolar choroidal nevi was 0 (Snellen equivalent, 20/20). The initial median±sd logmar visual acuity for extrafoveolar nevi was 0.09±0.22 (range, ); and for subfoveolar nevi, 0.20±0.35 (range, ). The final median±sd logmar visual acuity for extrafoveolar nevi was 0.14±0.31 (range, ); and for subfoveolar nevi, 0.34±0.53 (range, ). Of the 2334 patients with stable choroidal nevi who returned for a follow-up examination, the mean final logmar visual acuity for extrafoveolar choroidal nevi was 0.10 (Snellen equivalent, 20/25); and for subfoveolar choroidal nevi, 0.18 (Snellen equivalent, 20/30) (Figure 1). The mean follow-up was 5 years (range, 3 months to 36 years). Kaplan-Meier estimates of 3 lines of logmar visual acuity loss at 2, 5, 10, and 15 years are given in Table 2 and in Figure 2 and Figure 3. Table 2. Choroidal Nevus in 2334 Eyes: Comparison of Visual Acuity Loss of 3 or More LogMAR Lines in Extrafoveolar vs Subfoveolar Nevus Using Kaplan-Meier Estimates Location of the Choroidal Nevus Kaplan-Meier Estimates, % At2y At5y At10y At15y Extrafoveolar (n=2207) Subfoveolar (n=127) All choroidal nevi (N=2334) Abbreviation: logmar, logarithm of the minimum angle of resolution. The multivariate analyses for initial and final visual acuity of 20/50 to 20/100 and 20/200 in the entire group of 3422 eyes is listed in Table 3. The most important factors for poor final visual acuity of 20/200 included macular location of the nevus and overlying orange pigment, RE detachment, and foveal edema (Table 3). Factors predictive of loss of 3 or more logmar lines included reduced initial visual acuity of 20/50 (logmar, 0.4), subfoveolar location, juxtapapillary location, nevus thickness greater than 2 mm, related RE detachment, and foveal edema (Table 4). Factors predictive of intermediate (20/50-20/100 [logmar, ]) or poor (20/200 or worse [logmar, 1.0 ]) visual acuity at initial and final examination in eyes with subfoveolar choroidal nevus using multivariate analysis are listed in Table 5. In the 127 eyes with subfoveolar choroidal nevus for which the patient returned for a follow-up examination, factors predictive of loss of 3 or more log- MAR lines included Hispanic race, intermediate (20/50 ) initial visual acuity, and overlying orange pigment (Table 6). 1503

4 A B C D Figure 2. Clinical appearance of subfoveolar nevus with overlying retinal and retinal pigment epithelial (RE) changes and good long-term visual acuity. Subfoveolar choroidal nevus with overlying RE detachment and visual acuity of 20/20 at 18 months follow-up (A). Optical coherence tomographic (OCT) scan of the nevus in part A showing the foveola draped on the nasal margin of the RE detachment (B). Subfoveolar choroidal nevus with overlying orange pigment and a visual acuity of 20/20 at 22 months follow-up (C). The OCT scan of the nevus in part C showing the slight elevation of the foveola with optically dense material on the posterior retinal surface correlating with the orange pigment (D). COMMENT Choroidal nevus can lead to reduced central and peripheral visual acuity, depending on its location. Tamler and Maumenee 4 demonstrated visual field defects in 38% of 42 choroidal nevi, but remarked that it was not clear at that time how a choroidal nevus could affect the retinal function if the retina was not involved with tumor. Naumann and associates 9 later described a patient with paracentral scotoma from a choroidal nevus, found on histopathological examination to have loss of the outer retinal layers with complete loss of the rods and cones overlying the tumor. These findings sufficiently explained the symptomatic scotoma. Optical coherence tomography has been useful in further delineating the extent of retinal damage overlying choroidal nevus. Shields and associates 11 used OCT to analyze the retina overlying 120 consecutive choroidal nevi and found overlying retinal edema in 15%, photoreceptor thinning or complete absence in 51%, and general retinal thinning in 22%. 11 These in vivo OCT findings corroborated previous histopathological findings. 5,6,9 In the current analysis, we specifically analyzed subfoveolar vs extrafoveolar choroidal nevi to appreciate the comparative effects of tumor location on central visual acuity. Eyes with subfoveolar nevi composed 205 of the 3422 eyes (6.0%). A previous study 8 found subfoveal location of choroidal nevus in 28 of 375 patients (7.5%). At initial examination, eyes with subfoveolar choroidal nevus displayed a mean visual acuity of 20/20, similar to those with an extrafoveolar nevus. However, on final examination, eyes with a subfoveolar choroidal nevus had a slightly reduced mean visual acuity of 20/30 compared with 20/25 in those with an extrafoveolar nevus. The difference between these 2 groups was more remarkable when assessing loss of visual acuity over time, because 26% of the subfoveolar nevus group showed loss of 3 logmar lines of visual acuity by 15 years, whereas only 2% of the extrafoveolar group manifested a similar loss. In fact, eyes with a subfoveolar nevus had a 16 times higher RR for vision loss compared with eyes with an extrafoveolar nevus (Table 4). In the entire group of 2334 eyes with choroidal nevus for which the patient returned for follow-up, the most important factors for intermediate (20/50-20/100) or poor 1504

5 A B C D E F G H Figure 3. Clinical appearance of subfoveolar nevus with overlying retinal and retinal pigment epithelial (RE) changes and reduced long-term visual acuity. Subfoveolar choroidal nevus with overlying fibrous metaplasia of the RE and a visual acuity of 20/40 at 18 months follow-up (A). Optical coherence tomographic (OCT) scan of the nevus in part A showing thickening of the RE layer, particularly under the foveola, slight subretinal fluid, and diffuse optical density in the photoreceptor layer overlying the nevus, suggesting photoreceptor disruption (B). Subfoveolar choroidal nevus with overlying subtle orange pigment and a visual acuity of 20/25 at 51 months (C). The OCT scan of the nevus in part C showing overlying subretinal fluid and debris on the posterior retinal surface consistent with orange pigment (D). Circumpapillary subfoveolar choroidal nevus with subtle overlying orange pigment, mild fibrous metaplasia of the RE, and a visual acuity of counting fingers at 21 months follow-up (E). The OCT scan of the nevus in part E showing extensive confluent cystoid macular edema (F). Subfoveolar choroidal nevus with overlying fibrous metaplasia of the RE and a visual acuity of 20/100 at 52 months follow-up (G). The OCT of the nevus in part G showing dramatic cystoid macular edema (H). 1505

6 Table 3. Factors redictive of Intermediate or oor Visual Acuity at Initial and Final Examination in Eyes With Choroidal Nevus Using Multivariate Analysis a Clinical Factor Initial visual acuity of 20/50-20/100 Symptoms (decreased vision ( ).001 vs none b ) Anteroposterior location of nevus 6.80 ( ).001 epicenter (macula vs equator b ) Subretinal fluid over nevus Minimal vs none b 7.43 ( ).001 Moderate vs none b 4.57 ( ).008 Initial visual acuity of 20/200 Ultrasonographic acoustic 6.98 ( ).01 quality (hollow vs flat b ) Anteroposterior location of 7.68 ( ).02 nevus epicenter (macula vs equator b ) Subretinal fluid over nevus ( ).001 (moderate vs none b ) RE detachment over nevus ( ).02 Foveal edema (present ( ).001 vs absent b ) Final visual acuity of 20/50-20/100 Subretinal fluid over nevus Minimal vs none b 7.66 ( ).001 Moderate vs none b 5.19 ( ).002 Extensive vs none b ( ).001 Nevus location (subfoveal ( ).001 vs extrafoveal b ) Final visual acuity of 20/200 Nevus distance to foveola ( ).03 ( 3vs 3mm b ) Nevus quadratic location Macula vs inferior b 8.92 ( ).04 Macula vs temporal b ( ).002 Orange pigment over nevus 3.68 ( ).01 RE detachment over nevus ( ).003 Foveal edema ( ).001 Abbreviation: RE, retinal pigment epithelium. a There were 3422 eyes for the initial visual acuity data and 2334 eyes for the final visual acuity data. Intermediate visual acuity was 20/50 to 20/100 and poor visual acuity was 20/200. b Reference. (20/200 ) final visual acuity included subfoveolar nevus location and retinal or RE changes overlying the nevus, such as foveal edema, subretinal fluid, orange pigment, and RE detachment (Table 5). Similar to the previous results, subfoveolar location imparted a 21 times higher RR for intermediate final visual acuity and an 11 times higher RR for poor final visual acuity compared with extrafoveolar nevus (Table 3). Some of the related retinal and RE findings, such as subretinal fluid and orange pigment, that were associated with the visual outcome have also been shown in previous reports 13,14,16,18 to predict tumor growth into melanoma. In this analysis, only stable choroidal nevi without growth were included. Table 4. Factors redictive of Visual Acuity Loss of 3 or More LogMAR Lines in 2334 Eyes With Choroidal Nevus Using Multivariate Analysis Clinical Factor Initial visual acuity of 20/ ( ).001 (present vs absent a ) Nevus distance to optic nerve 4.52 ( ).008 (0 vs 0mm a ) Nevus distance to foveola ( ).001 (0 vs 0mm a ) Nevus thickness ( 2vs 2mm a ) 3.89 ( ).009 RE detachment over nevus ( ).001 (present vs absent a ) Foveal edema (present vs absent a ) 9.02 ( ).002 Abbreviations: logmar, logarithm of the minimum angle of resolution; RE, retinal pigment epithelium. a Reference. Table 5. Factors redictive of Intermediate or oor Visual Acuity at Initial and Final Examination in Eyes With Subfoveolar Choroidal Nevus Using Multivariate Analysis a Clinical Factor Initial visual acuity of 20/50-20/100 Subretinal fluid over nevus Minimal vs none b ( ).02 Moderate vs none b ( ).01 Initial visual acuity of 20/200 RE fibrous metaplasia 6.96 ( ).03 Final visual acuity of 20/50-20/100 Age ( 65yvs 65 y b ) 4.35 ( ).01 Initial visual acuity of 20/ ( ).003 Nevus thickness 4.93 ( ).01 ( 2vs 2mm b ) Choroidal neovascularization ( ).003 over nevus (present vs absent b ) Final visual acuity of 20/200 Decreased vision vs none b ( ).03 Flashes or floaters vs none b ( ).03 Initial visual acuity of 20/ ( ).006 (present vs absent b ) Nevus distance to optic nerve (0 vs 0mm b ) 4.13 ( ).04 Abbreviation: RE, retinal pigment epithelium. a There were 205 eyes for the initial visual acuity data and 127 eyes for the final visual acuity data. Intermediate visual acuity was 20/50 to 20/100 and poor visual acuity was 20/200. b Reference. Based on published OCT data, retinal and RE alterations are fairly common overlying choroidal nevi and these features could translate to visual field loss if the nevus is extrafoveal and central vision loss if the nevus is subfoveal. In the current analysis of all 2334 eyes with 1506

7 Table 6. Factors redictive of Visual Acuity Loss of 3 or More LogMAR Lines in 127 Eyes With Subfoveolar Choroidal Nevus Clinical Factors a Race (Hispanic vs white a ) ( ).002 Initial visual acuity of 20/ ( ).008 (present vs absent a ) Orange pigment (present vs absent a ) 4.36 ( ).008 Abbreviation: LogMAR, logarithm of the minimum angle of resolution. a Reference. choroidal nevus, the most important factor for poor final visual acuity was foveal edema, which imparted a 19 times RR (Table 3), and the most important factor for visual acuity loss was overlying RE detachment, which imparted a 22 times RR (Table 4). Most of the information on the foveal features in our study, which extends over 4 decades, was gathered by clinical examination; and only a few patients underwent OCT imaging of the fovea. Related clinical features, such as RE detachment, can be difficult to visualize clinically. In an analysis of OCT findings of 120 patients with choroidal nevi, RE detachment overlying the nevus was found on OCT in 12% of cases, whereas it was visualized clinically in only 2%. 11 Optical coherence tomography could be beneficial in estimating risks for poor visual outcome. This analysis focused on visual results in a large cohort of 3422 consecutive patients with choroidal nevus. The results, however, could be biased toward larger or thicker nevi because many patients were referred to this ocular oncology center with the diagnosis of possible small choroidal melanoma vs choroidal nevus. In this cohort, the mean nevus diameter was 5.1 mm and the mean nevus thickness was 1.6 mm. In comparison, Sumich and associates 3 analyzed 264 choroidal nevi and found a mean nevus diameter of 1.25 mm (thickness not recorded). In summary, central visual acuity can be diminished in eyes with choroidal nevus, particularly if the nevus is subfoveolar and there are related retinal and RE alterations affecting the foveola. atients with subfoveolar choroidal nevi should be forewarned that visual acuity could decrease slowly over time. Submitted for ublication: March 1, 2007; final revision received April 17, 2007; accepted April 19, Correspondence: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Institute, 840 Walnut St, Ste 1440, hiladelphia, A (carol.shields@shieldsoncology.com). Author Contributions: Dr C. L. Shields had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Financial Disclosure: None reported. Funding/Support: This study was supported by the Retina Research Foundation, Charles L. Schepens Lecture of the Retina Society, Capetown, South Africa (Dr C. L. Shields); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust, hiladelphia, ennsylvania (Dr C. L. Shields); the LuEsther Mertz Retina Research Foundation, New York, New York (Dr C. L. Shields); a donation from Michael, Bruce, and Ellen Ratner, New York (Drs C. L. Shields and J. A. Shields); the Eye Tumor Research Foundation, hiladelphia (Drs C. L. Shields and J. A. Shields); and the aul Kayser International Award of Merit in Retina Research, Houston, Texas (Dr J. A. Shields). revious resentation: This study was presented at the International Congress of Ocular Oncology; June 29, 2007; Siena, Italy. Additional Contributions: Rishita Nutheti, International Centre for Advancement of Rural Eye Care, L. V. rasad Institute, Hyderabad, India, performed the statistical analysis. REFERENCES 1. Shields JA, Shields CL. Choroidal nevus. In: Shields JA, Shields CL, eds. Intraocular Tumors: A Text and Atlas. hiladelphia, A: WB Saunders Co; 1992: Shields JA, Shields CL. Choroidal nevus. In: Shields JA, Shields CL, eds. 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