Intraoperative Retinal Changes May Predict Surgical Outcomes After Epiretinal Membrane Peeling.

Purpose: To investigate whether intraoperative retinal changes during epiretinal membrane (ERM) peeling affect anatomic or functional outcomes after surgery. Methods: We measured retinal thickness using an intraoperative optical coherence tomography (iOCT) device in patients undergoing pars plana vitrectomy with membrane peeling for idiopathic ERM. Changes in intraoperative central macular thickness (iCMT) were compared with postoperative improvements in CMT and best-corrected visual acuity (VA). Results: Twenty-seven eyes from 27 patients (mean age 68 years) underwent iOCT-assisted ERM peeling surgery. Before surgery, mean VA was logMAR 0.50 ± 0.36 (Snellen 20/63), and mean baseline CMT was 489 ± 82 µm. Mean iCMT before peeling was 477 ± 87 µm, which correlated well with preoperative CMT (P < 0.001). Mean change in iCMT was -39.6 ± 37 µm (range -116 to +77 µm). After surgery, VA improved to logMAR 0.40 ± 0.38 (Snellen 20/50) at month 1 and logMAR 0.27 ± 0.23 (Snellen 20/37) at month 3, whereas CMT decreased to 397 ± 44 µm and 396 ± 51 µm at months 1 and 3. Eyes that underwent greater amount of iCMT change (absolute value of iCMT change) were associated with greater CMT reduction at month 1 (P < 0.001) and month 3 (P = 0.010), whereas those with greater intraoperative thinning (actual iCMT change) showed a trend toward better VA outcomes at months 1 (P = 0.054) and 3 (P = 0.036). Conclusions: Intraoperative changes in retinal thickness may predict anatomic and visual outcomes after idiopathic ERM peeling surgery. Translational Relevance: Our study suggests that intraoperative retinal tissue response to ERM peeling surgery measured by iOCT may be a prognostic indicator for restoration of retinal architecture and for visual acuity outcomes.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

UVEAL METASTASIS BASED ON PATIENT AGE IN 1,111 PATIENTS: Comparison of Clinical Features and Outcomes Per Age Category.

PURPOSE: To evaluate clinical features and survival outcomes of uveal metastasis based on patient age. METHODS: Retrospective analysis of all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017. The features and outcomes were analyzed based on patient age classified as children (0-20 years), young adults (21-40 years), middle [aged] adults (41-60 years), older adults (61-80 years) and senior adults (81-100 years). RESULTS: There were 1111 consecutive patients, including children (n = 3, <1%), young adults (n = 77, 7%), middle adults (n = 472, 42%), older adults (n = 509, 46%), and senior adults (n = 50, 4%). At uveal metastasis diagnosis, demographics included mean patient age of 60 years, Caucasian race (88%), and female gender (64%). Compared to the largest cohort (older adults), there were significant differences (age group versus [vs.] older adults) in Caucasian race (senior adult 98% vs. 89%, p = 0.042), male sex (young adults: 22% vs. 43%, p < 0.001) (middle adults: 29% vs. 43%, p < 0.001), unilateral tumor (young adult: 70% vs. 86%, p < 0.001) (middle adult: 79% vs. 86%, p = 0.003) (senior adults: 96% vs. 86%, p = 0.045), and cancer origin in breast (young adults: 51% vs. 32%, p = 0.002) (middle adults: 44% vs 32%, p < 0.001), lung (young adults: 14% vs. 30%, p = 0.004), kidney (young adults: 0% vs. 5%, p = 0.043), prostate (middle adults: 1% vs. 4%, p = 0.001), gastrointestinal tract (senior adults: 8% vs. 2%, p = 0.028), and others (children: 100% vs. 4%, p < 0.001) (young adults: 10% vs. 4%, p = 0.044). Kaplan-Meier survival (children, young, middle, older, and senior adults) at 1 year was 33%, 48%, 60%, 62%, and 76% and at 5 years was 0%, 22%, 29%, 25%, and 40%, respectively, with no difference per age category. The mean overall survival was 17.2 months and children demonstrated hazard ratio (HR) for death at 1 year of 2.1 relative to older adults. CONCLUSION: Uveal metastasis is found in all age groups. Compared to older adults, primary cancer site was more often breast and less likely lung in young and middle adults. Other rare sites were more often seen in children. Survival outcomes at 1 and 5 years were most favorable for senior adults and least favorable for children.

Identification of Patients with Pentosan Polysulfate Sodium-Associated Maculopathy through Screening of the Electronic Medical Record at an Academic Center.

AIMS: This chart review of a quaternary academic medical center electronic medical record (EMR) aimed to identify patients at risk of development of maculopathy with exposure to pentosan polysulfate sodium (PPS). METHODS: A review of electronic medical records of a quaternary medical center of patients with either documented exposure to PPS or diagnosis of interstitial cystitis (IC) from 2007 to 2019 was performed for retinal imaging and visual acuity; the study was conducted in August of 2019. RESULTS: 216 charts were included for analysis, of which 96 had documented eye exams and 24 had retinal imaging done. We identified three patients with maculopathy in the context of long-term exposure to PPS via chart review, and one additional patient was identified by referral. The median PPS exposure duration was 11 years (range 7 to 19 years). Median logMAR BCVA OD 0.6 range was 0.0-1.9 (approximate Snellen equivalent 20/80 range (20/20-20/1600)) and OS 0.7 range was 0.1-1.9 (approximate Snellen equivalent 20/100 range (20/25-20/1600)). Ultrawidefield color fundus imaging and fundus autofluorescence revealed findings of pigmentary changes and patchy macular atrophy. Optical coherence tomography (OCT) demonstrated outer retinal thinning and increased choroidal transmission coincident with areas of atrophy seen on fundus imaging. CONCLUSIONS: Less than half of patients at risk for development of maculopathy due to exposure to PPS had received eye examinations, suggesting that those at risk are not receiving adequate screening. We found two patients with PPS maculopathy who had relatively preserved central vision, one patient with bitemporal vision loss, and one patient who developed vision loss in both eyes.

Choroidal amelanotic tumours: clinical differentiation of benign from malignant lesions in 5586 cases.

PURPOSE: To investigate demographics and clinical features of patients with amelanotic choroidal tumours. DESIGN: Retrospective analysis. METHODS: Comparison of demographic and clinical features of various amelanotic choroidal tumours based on stratification by patient age, sex and tumour diameter. Included were all patients with amelanotic choroidal tumours evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA, over a 45-year time period. RESULTS: A total of 5586 amelanotic choroidal tumours in 4638 eyes of 4441 patients were included with a mean age at presentation of 58 years (median 60, range 0.1-100 years). Most patients were white (95%), female (56%) and with unilateral lesion (96%). By comparison, amelanotic melanoma presented at a younger mean age (57 years) compared with metastasis (60 years, p<0.001), nevus (61 years, p<0.001), lymphoma (65 years, p<0.001), sclerochoroidal calcification (70 years, p<0.001) and peripheral exudative haemorrhagic chorioretinopathy (80 years, p<0.001). Melanoma presented at an older mean age compared with osteoma (30 years, p<0.001), granuloma (42 years, p<0.001), haemangioma (49 years, p<0.001) and inflammatory choroidal lesions (49 years, p<0.001). Differences in race and sex were also seen between the various amelanotic choroidal lesions. With few exceptions, amelanotic melanoma had significantly larger basal diameter, greater thickness, more frequent association with subretinal fluid and more often ultrasonographically hollow, compared with other amelanotic choroidal lesions. CONCLUSION: Understanding the demographic and clinical features of amelanotic choroidal melanoma and other amelanotic lesions could lead to an earlier and more accurate diagnosis.

HAND-HELD OPTICAL COHERENCE TOMOGRAPHY MONITORING OF CHEMORESISTANT RETINOBLASTOMA.

PURPOSE: Retinoblastoma (Rb) is a potentially fatal intraocular malignancy in children, and hand-held optical coherence tomography (HH-OCT) can assist in submillimeter detection and monitoring after treatment of Rb. Retinoblastoma located in the macula, or those with chemoresistance, can be among the most difficult to manage. We describe HH-OCT features in a case of chemoresistant macular Rb that eventually responded to plaque radiotherapy after failing intravenous chemotherapy and intraarterial chemotherapy. METHODS: Observational case report. RESULTS: A 15-month-old girl with leukocoria was found to have Group D Rb in the right eye of 6-mm thickness and macular Group B Rb in the left eye of 4-mm thickness. She was treated with 6-monthly cycles of systemic intravenous chemotherapy and focal consolidation therapies to both eyes, with tumor regression in both eyes. However, macular tumor in the left eye demonstrated subsequent recurrence, from regressed thickness of 792 µm on HH-OCT to a dome-shaped hyperreflective retinal mass of >2000 µm thickness. Three cycles of intraarterial chemotherapy were sufficient for tumor regression down to 977 µm thickness on HH-OCT. Six months later, macular tumor in the left eye recurred again to >2000 µm thickness and necessitated plaque radiotherapy using apex dose of 35 Gy over 95.25 hours. Hand-held OCT confirmed rapid tumor regression to 722 µm after plaque treatment and regression remained stable at 6-month follow-up. CONCLUSION: Hand-held OCT was critical in assessment of Rb after failed intravenous chemotherapy and intraarterial chemotherapy and later documenting regression after plaque radiotherapy. Hand-held OCT is vital in providing cross-sectional imaging and measurements of small macular and paramacular Rbs.

Spectral-Domain OCT Predictors of Visual Outcomes after Ranibizumab Treatment for Macular Edema Resulting from Retinal Vein Occlusion.

PURPOSE: To evaluate spectral-domain (SD)-OCT features associated with baseline vision and visual outcomes in the prospective, multicenter Study Evaluating Dosing Regimens for Treatment with Intravitreal Ranibizumab Injections in Subjects with Macular Edema following Retinal Vein Occlusion (SHORE). DESIGN: Post hoc analysis of prospective clinical trial data. PARTICIPANTS: Two hundred two participants in the 15-month, phase 4 SHORE study comparing monthly versus pro re nata ranibizumab after 7 monthly doses in eyes with retinal vein occlusion (RVO) with macular edema. METHODS: Baseline SD-OCT images were assessed for (1) central subfield thickness (CST); (2) presence of vitreomacular adhesion, vitreomacular traction, or epiretinal membrane; (3) presence, location, and amount of intraretinal fluid or subretinal fluid (SRF); (4) presence, location, and amount of hyperreflective foci (HF); (5) disorganization of retinal inner layers (DRIL); and (6) disruption of external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Univariate and multivariate regression analyses were performed to evaluate the association of these features with baseline best-corrected visual acuity (BCVA) and change in BCVA after 7 monthly ranibizumab injections. MAIN OUTCOME MEASURES: Association of SD-OCT features with baseline BCVA and change in BCVA after 7 monthly ranibizumab injections. RESULTS: Before therapy, worse baseline BCVA was associated with ERM presence (P = 0.0045), thicker SRF (P = 0.0006), larger intraretinal cysts (P = 0.0015), and higher percentage of DRIL (P < 0.0001), percentage of ELM disruption (P < 0.0001), percentage of EZ disruption (P = 0.0003), and percentage of IZ disruption (P = 0.0018). In multivariate models, only percentage of ELM disruption independently impacted baseline BCVA (P < 0.0001). After 7 monthly ranibizumab injections, mean BCVA improved by 18.3±12.6 Early Treatment Diabetic Retinopathy Study letters in treated eyes. The only factors independently associated with BCVA gain after 7 monthly ranibizumab treatments were younger age (P < 0.0001) and worse baseline BCVA (P < 0.0001). CONCLUSIONS: Although SD-OCT features may be associated with presenting vision in eyes with macular edema and RVO, most eyes treated with ranibizumab achieve substantial vision gains, and only older age and better baseline BCVA limited visual improvements.

Management of retinoblastoma in older children (>5 years) using intra-arterial chemotherapy: Comparison of outcomes to prechemotherapy and intravenous chemotherapy eras.

Purpose: Intra-arterial chemotherapy (IAC) has emerged as an effective treatment for retinoblastoma (RB) however, little information exists regarding its use in older patients (>5 years). In the present study, we evaluate the use of IAC (2008-2018) for RB in older patients and compare the outcomes to those in the prechemotherapy (<1994) and intravenous chemotherapy (IVC) (1994-2007) eras. Methods: A retrospective analysis of all patients older than 5 years treated with IAC for RB from 2008-2018. Comparisons were made to 26 active RB cases in older children treated in the prechemotherapy era and to 12 active RB cases treated in the IVC era. Results: There were 13 eyes with RB in 13 older patients treated in the IAC era. The median patient age was 6.8 years. Tumor response was achieved in all 13 eyes at a median interval of 1.1 months from first IAC. Globe salvage was achieved in eight eyes with five eyes requiring enucleation. At 14 months, median follow-up after IAC, there was no metastasis or death. Compared to the prechemotherapy era, those in the IAC era demonstrated significant reduction in need for enucleation (P < 0.001) and EBRT or enucleation (P < 0.001). Compared to the IVC era, there was significant reduction in need for EBRT (P = 0.02) and EBRT or enucleation (P = 0.03) and similar avoidance of metastasis (P > 0.99) and death (P > 0.99). Conclusion: Older patients with RB managed in the IAC era demonstrated reduced need for EBRT or enucleation compared to those managed in the IVC or prechemotherapy eras, with no instance of metastasis or death.

Uveal metastasis in 1111 patients: Interval to metastasis and overall survival based on timing of primary cancer diagnosis.

PURPOSE: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis. METHODS: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2 years with differences in primary sites of gastrointestinal (2.1 years, p = 0.003), lung (2.2 years, p < 0.001), breast (6.5 years, p < 0.001), and thyroid (13 years, p < 0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis. CONCLUSION: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.

Retinoblastoma regression following intra-arterial chemotherapy to the contralateral eye.

Intra-arterial chemotherapy (IAC) has assumed a major role in the management of retinoblastoma. This targeted therapy involves the delivery of chemotherapy directly into the ophthalmic artery, minimizing systemic absorption. We report a case of retinoblastoma regression in the untreated eye following IAC to the contralateral eye.

Uveal Metastasis Based on Patient Sex in 2214 Tumors of 1111 Patients. A Comparison of Female Versus Male Clinical Features and Outcomes.

BACKGROUND: Lacking in previous studies on uveal metastasis is a robust statistical comparison of patient demographics, tumor features, and overall survival based on patient sex. OBJECTIVE: The aim of this study was to evaluate demographics, clinical features, and overall survival of patients with uveal metastasis based on sex. METHOD: This is a retrospective analysis. All patients were evaluated on the Ocular Oncology Service, Wills Eye Hospital, PA between January 1, 1974 and June 1, 2017. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. A comparison (female versus male) revealed differences across several demographic and clinical features including, among others, mean age at metastasis diagnosis (58 vs 63 years, P < 0.001), bilateral disease (21% vs 11%, P < 0.001), and mean number of metastases per eye (1.8 vs 1.6 tumors per eye, P = 0.04). There were differences in overall mean survival (20 vs 13 months, P = 0.03) and 5-year survival (Kaplan-Meier estimate) (31% vs 21%, P < 0.001). CONCLUSIONS: There are demographic, clinical, and survival differences when patients with uveal metastases are compared by sex. Understanding these differences can aid the clinician in better anticipating patient outcomes.

Precision Intravitreal Chemotherapy for Localized Vitreous Seeding of Retinoblastoma.

PURPOSE: To describe and evaluate the effectivity of a novel precision intravitreal injection technique for select cases of localized vitreous seeding in retinoblastoma. METHODS: Patients with localized vitreous seeds from retinoblastoma received intravitreal chemotherapy via a precision injection technique (P-IVitC) intended to optimize local delivery of melphalan to target seeds. The needle was inserted trans-pars plana and chemotherapy deposited within 3 mm of the target seed(s) under indirect ophthalmoscopic guidance. Without subsequent globe manipulation, the head was then positioned to promote gravity-dependent settling of chemotherapy. RESULTS: There were 8 eyes of 8 patients treated with P-IVitC for active vitreous seeds following adequate solid tumor control with intravenous chemotherapy (n = 3, 38%) or intra-arterial chemotherapy (n = 5, 63%). Viable vitreous seeds were primarily solitary spheres (n = 6, 75%) and measured an average of 2.7 mm in diameter. Vitreous seed resolution (n = 8, 100%) was noted after a mean of 2.6 injections (median 2; range 1-3) of 20 µg melphalan. There was no recurrence at a mean follow-up of 10.0 months. Only 1 eye had an associated complication (focal retinal pigment epithelial mottling, n = 1, 13%). CONCLUSIONS: With direct delivery of chemotherapy to within 3-4 mm of vitreous seed activity, P-IVitC provided complete control of localized vitreous seeds with minimal toxicity.

Ultrasonography and transillumination for uveal melanoma localisation in proton beam treatment planning.

BACKGROUND/OBJECTIVE: The success of proton beam treatment (PBT) in uveal melanoma depends in part on the accuracy of tumour localisation. This study determined if using ultrasonography (US) to measure the distance between tumour margin and tantalum ring (DTR) in PBT planning improves local treatment success when compared with using intraoperative transillumination (TI) alone. METHODS: Retrospective analysis of patients with uveal melanoma treated at one centre between January 2006 and June 2017 with ≥12-month follow-up (or until treatment failure). Local tumour control was compared among study groups based on methods for measuring DTR: Group 1 (TI alone), Group 2A (postoperative US alone) and Group 2B (combination). RESULTS: Fifty-four eyes (54 patients) with uveal melanomas were included: Group 1 (22 eyes, 41%), Group 2A (11 eyes, 20%) and Group 2B (21 eyes, 39%). Mean age at diagnosis was 64 years [median 66 years, range 23-86 years]. Fifty tumours (93%) involved the choroid, while four involved the ciliary body (7%). In Group 2B, PBT treatment was based on the DTR obtained using US; DTR differed between TI and US by ≥1 mm for 25 rings in 16 eyes and ≥2 mm for 12 rings in 7 eyes. Five-year Kaplan-Meier estimate revealed a difference in local treatment success between Groups 1 and 2, (0.82 vs. 1.0, p = 0.02) with no difference in overall survival estimate, (0.85 vs. 0.83, p = 0.8). CONCLUSIONS: US can be used to measure DTR in PBT planning for uveal melanoma. This may improve accuracy of tumour localisation and improve local treatment success.

CHOROIDAL NEVUS TRANSFORMATION INTO MELANOMA PER MILLIMETER INCREMENT IN THICKNESS USING MULTIMODAL IMAGING IN 2355 CASES: The 2019 Wendell L. Hughes Lecture.

PURPOSE: To analyze risk of nevus transformation into melanoma per millimeter increment. METHODS: Retrospective analysis of 3,806 choroidal nevi for transformation into melanoma per incremental millimeter thickness (flat [≤1.0 mm], thin [1.1-2.0 mm], thicker [2.1-3.0 mm], and thickest [>3.0 mm]) RESULTS:: The median nevus thickness was 1.4 mm, and nevi were categorized (flat, thin, thicker, and thickest) in 1,140 (30%), 2052 (54%), 555 (15%), and 59 (<1%), respectively. There were differences in tumor diameter (2.5, 4.8, 7.5, and 9.3 mm; P < 0.01), optical coherence tomography detection of overlying subretinal fluid (<1, 4, 15, and 11%; P < 0.01), overlying retinal edema (<1, 3, 14, and 25%; P < 0.01), overlying drusen (23, 49, 64, and 64%; P < 0.01), overlying retinal pigment epithelial detachment (1, 4, 4, and 9%; P < 0.01), and overlying lipofuscin hyperautofluoresence (<1, 3, 6, and 7%; P < 0.01). Choroidal nevus transformation into melanoma (n = 90/2,355 cases, 3.8%) was found by Kaplan-Meier 7-year estimates (2.2, 6.1, 31.7, and 34.5%; P < 0.0001) and by hazard ratio (HR) compared with nevus ≤1.0 mm (not available, 4.7 [P = 0.01], 35.7 [P < 0.0001], and 52.0 [P < 0.0001]). For all thicknesses, those with growth displayed increase in mean basal diameter of 2.4 mm and thickness of 1.1 mm, optical coherence tomography increase in subretinal fluid (65%), autofluorescence increase in lipofuscin (40%), and ultrasonography increase in hollowness (30%). Multivariable risk factors, recalled by the mnemonic "To Find Small Ocular Melanoma Doing IMaging" (TFSOM-DIM) representing Thickness >2 mm (ultrasonography), Fluid subretinal (optical coherence tomography), Symptom vision loss (Va), Orange pigment (autofluorescence), Melanoma hollow (ultrasonography), and DIaMeter >5 mm, revealed factors per incremental thickness category (compared with flat) including thin (Fluid overlying, HR 6.1; DIaMeter >5 mm, HR 3.3), thicker (Fluid subretinal ≤3 mm from nevus, HR 5.7; Melanoma acoustic hollowness, HR 2.7), and thickest (Orange pigment, HR 9.1). CONCLUSION: Each incremental increase in choroidal nevus thickness demonstrated risk of growth into melanoma with HR (compared with flat) 4.7 for thin, 35.7 for thicker, and 52.0 for thickest. The increase from ≤2.0 mm to >2.0 mm thickness conferred the greatest rise for transformation.

CHOROIDAL NEVUS IMAGING FEATURES IN 3,806 CASES AND RISK FACTORS FOR TRANSFORMATION INTO MELANOMA IN 2,355 CASES: The 2020 Taylor R. Smith and Victor T. Curtin Lecture.

PURPOSE: To use multimodal imaging for identification of risk factors for choroidal nevus transformation into melanoma. METHODS: Retrospective chart review of 3806 consecutive choroidal nevi with imaging and 2355 choroidal nevi with additional follow up to identify factors predictive of transformation of choroidal nevus into melanoma. RESULTS: The median patient age was 62.5 years and Caucasian race in 3167 (95%). The choroidal nevus demonstrated median basal diameter of 4.0 mm and thickness of 1.4 mm. Imaging included optical coherence tomography (OCT) showing subretinal fluid (SRF) in 312 (9%), ultrasonography (US) with acoustic hollowness in 309 (9%), and hyper-autofluorescence (AF) in 100 (3%). Of those 2355 choroidal nevi with follow up, Kaplan-Meier estimates of nevus transformation into melanoma at 1, 5, and 10 years were 1.2%, 5.8%, and 13.9%, respectively. Multivariate analysis, using multimodal imaging for detection of factors predictive of nevus transformation into melanoma, included thickness >2 mm on US (hazard ratio (HR) 3.80, p < 0.0001), SRF on OCT as cap over nevus (HR 3.00, p < 0.0001) or SRF ≤3 mm from nevus margin (HR 3.56, p = 0.0003), symptomatic vision loss ≤20/50 on Snellen visual acuity (VA) (HR 2.28, p = 0.005), orange pigment (lipofuscin) hyperautofluorescence on AF (HR 3.07, p = 0.0004), acoustic hollowness on US (HR 2.10, p = 0.0020), and tumor diameter >5 mm on photography (HR 1.84, p = 0.0275). These factors can be recalled by the mnemonic "To Find Small Ocular Melanoma Doing IMaging" (TFSOM-DIM) representing Thickness >2 mm (US), Fluid subretinal (OCT), Symptoms vision loss (VA), Orange pigment (AF), Melanoma hollow (US), and DIaMeter >5mm (photography). The mean 5-year estimates of nevus growth into melanoma were 1% (HR 0.8) for those with 0 risk factor, 11% (HR 3.09) with 1 factor, 22% (HR 10.6) with 2 factors, 34% (HR 15.1) with 3 factors, 51% (HR 15.2) with 4 factors, 55% (HR 26.4) with 5 risk factors, and not-estimable with all 6 risk factors. CONCLUSION: In this analysis, multimodal imaging was capable of detecting risk factors for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for transformation.

CHOROIDAL MELANOMA, SECTOR MELANOCYTOSIS, AND RETINAL PIGMENT EPITHELIAL MICRODETACHMENTS IN BIRT-HOGG-DUBÉ SYNDROME.

PURPOSE: Birt-Hogg-Dubé Syndrome (BHDS) is a rare autosomal dominant condition that can predispose patients to numerous cutaneous fibrofolliculomas and other cutaneous lesions, pulmonary cysts with spontaneous pneumothorax, and multifocal renal tumors and cancer. The genetic mutations responsible for BHDS are related to tumor suppression and the mammalian target of rapamycin (mTOR) pathway. Previous reports of the ocular findings in BHDS include eyelid fibrofolliculomas, "flecked chorioretinopathy," and one report of choroidal melanoma. We report a patient with BHDS who presented with choroidal melanoma, sector melanocytosis, and retinal pigment epithelial microdetachments. METHODS: Observational case report. RESULTS: A 38-year-old man with BHDS manifesting with facial fibrofolliculomas/tricodiscomas and pulmonary cysts with previous pneumothorax of both lungs was noted to have a large choroidal nevus, managed with observation elsewhere. On referral 1 year later, photopsia and visual field defect were noted, and the patient was discovered to have subtle patchy sector ocular melanocytosis of the iris and choroid with choroidal melanoma and dependent subretinal fluid. The melanoma measured 14 mm in basal dimension and 6.8 mm in thickness. In addition, pinpoint retinal pigment epithelial microdetachments were observed in both eyes at the equator and confirmed on optical coherence tomography. Custom-fit plaque radiotherapy was provided for tumor control. CONCLUSION: The BHDS can be associated with tumors of the skin and kidney. In this case, we noted ocular melanocytosis, malignant choroidal melanoma, and bilateral pinpoint retinal pigment epithelial detachments.