Optical coherence tomography angiography in diabetic retinopathy: A major review.

Diabetic retinopathy (DR) is characterized by retinal vasculopathy and is a leading cause of visual impairment. Optical coherence tomography angiography (OCTA) is an innovative imaging technology that can detect various pathologies and quantifiable changes in retinal microvasculature. We briefly describe its functional principles and advantages over fluorescein angiography and perform a comprehensive review on its clinical applications in the screening or management of people with prediabetes, diabetes without clinical retinopathy (NDR), nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME). OCTA reveals early microvascular alterations in prediabetic and NDR eyes, which may coexist with sub-clinical neuroretinal dysfunction. Its applications in NPDR include measuring ischemia, detecting retinal neovascularization, and timing of early treatment through predicting the risk of retinopathy worsening or development of DME. In PDR, OCTA helps characterize the flow within neovascular complexes and evaluate their progression or regression in response to treatment. In eyes with DME, OCTA perfusion parameters may be of predictive value regarding the visual and anatomical gains associated with treatment. We further discussed the limitations of OCTA and the benefits of its incorporation into an updated DR severity scale.

Early Sign of Retinal Neovascularization Evolution in Diabetic Retinopathy: A Longitudinal OCT Angiography Study.

Purpose: To assess whether the combination of en face OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR). Design: Retrospective, longitudinal study. Participants: Patients with DR that had at least 2 visits. Methods: We obtained wide-field OCTA scans of 1 eye from each participant and generated en face OCT, en face OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on en face OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on en face OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the en face OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV. Main Outcome Measures: The characteristics and longitudinal observation of early signs of RNV. Results: From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age (P = 0.014) and tended to be treatment naive (P = 0.07) compared with eyes without progression. Conclusions: Longitudinal observation demonstrated that a combination of en face OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on en face OCTA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Inverted ILM Flap Technique in Optic Disc Pit Maculopathy.

Purpose: To present the outcome of optic disc pit maculopathy (ODPM) managed successfully with an inverted internal limiting membrane (ILM) flap over the optic disc. A narrative review of ODPM pathogenesis and surgical management techniques are also provided. Case Report: This prospective interventional case series included three eyes of three adult patients (25-39 years old) with unilateral ODPM and a mean duration of unilaterally decreased visual acuity of 7.33 ± 2.40 months (4-12 months). The pars plana vitrectomy with posterior vitreous detachment induction was performed on eyes, followed by an inverted ILM flap insertion over the optic disc and gas tamponade. Patients were followed for 7-16 weeks postoperatively; best-corrected visual acuity (BCVA) improved dramatically in one patient from 2/200 to 20/25. BCVA in other patients improved two and three lines - to 20/50 and 20/30, respectively. A significant anatomical improvement was achieved in all three eyes, and no complication was detected throughout the follow-up period. Conclusion: Vitrectomy with inverted ILM flap insertion over the optic disc is safe and can yield favorable anatomical improvement in patients with ODPM.

Utility of En Face OCT for the Detection of Clinically Unsuspected Retinal Neovascularization in Patients with Diabetic Retinopathy.

PURPOSE: To assess the value of en face OCT for detecting clinically unsuspected retinal neovascularization (RNV) in patients with nonproliferative diabetic retinopathy (NPDR). DESIGN: A retrospective, cross-sectional study. PARTICIPANTS: Treatment-naïve patients clinically graded as NPDR in an ongoing prospective observational OCT angiography (OCTA) study at a tertiary care center. METHODS: Each patient underwent imaging of 1 eye with a spectral-domain OCTA, generating a 17 × 17-mm widefield image by montaging four 9 × 9-mm scans. Two independent graders examined a combination of en face OCT, en face OCTA with a custom vitreoretinal interface slab, and cross-sectional OCTA to determine the presence of RNV. We measured the area of RNV flow within RNV lesions on en face OCTA. MAIN OUTCOME MEASURES: Detection rate of clinically occult RNV with OCT and OCTA. RESULTS: Of 63 enrolled eyes, 27 (43%) were clinically graded as severe NPDR, 16 (25%) as moderate NPDR, and 20 (32%) as mild NPDR. Using the combination of en face OCT, en face OCTA, and cross-sectional OCTA, the graders detected 42 RNV lesions in 12 (19%) eyes, of which 8 (67%) were graded as severe NPDR, 2 (17%) as moderate NPDR, and 2 (17%) as mild NPDR. The sensitivity of en face OCT alone for detecting eyes with RNV was similar to that of en face OCTA alone (100% vs. 92%; P = 0.32), whereas the specificity of en face OCT alone was significantly lower than that of en face OCTA alone (32% vs. 73%; P < 0.001). For detecting individual RNV lesions, the en face OCT was 100% sensitive, compared with 67% sensitivity for the en face OCTA (P < 0.001). The area of RNV lesions that manual grading with en face OCTA alone missed was significantly smaller than that of manually detectable RNV (Mean [standard deviation] RNV flow area, 0.015 [0.020] mm2 vs. 0.16 [0.36] mm2; P < 0.001). CONCLUSION: The combination of en face OCT and OCTA can detect clinically occult RNV with high sensitivity. For screening these small lesions, en face OCT may be a useful imaging modality. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Retinal ischemic cascade: New insights into the pathophysiology and imaging findings.

Retinal ischemia gives rise to a complex spectrum in which the cumulative profile of ischemia of the middle and inner retina can be highly variable. We reviewed the current knowledge on paracentral acute middle maculopathy (PAMM) pathophysiology and accompanying risk factors, the middle and inner retinal vasculature and blood flow, and the vulnerability of the middle retina in vaso-occlusive disorders. The inner nuclear layer (INL) is easily affected by slight degrees of retinal hypoperfusion and ischemia. INL infarction starts at perivenular sites, manifesting as skip PAMM lesions and a fern-like appearance in cross-sectional and en face views, respectively. With horizontal progression, INL infarction may develop into diffuse globular PAMM. If vertical progression occurs, the entire middle and inner portions of the retina can be affected. Transmural infarction of the middle and inner retina would be at the end of this spectrum. This gradient of ischemic progression resembles an ischemic cascade. We review the evidence supporting the term "retinal ischemic cascade," which encompasses a broad continuum of manifestations with roots in middle retinal infarction. With this terminology, variations in spatial and temporal progression and resolution of ischemia can also be delivered; it further enables addressing the possible associations between the middle and inner retinal ischemic patterns.

Erratum: Inverted ILM Flap Technique in Optic Disc Pit Maculopathy.

[This corrects the article DOI: 10.18502/jovr.v18i2.13189.].

Ruthenium-106 plaque radiotherapy for uveal melanoma: analysis of tumor dimension and location on anatomical and functional results.

BACKGROUND: To report the long-term outcomes of Ru-106 plaque radiotherapy in eyes with uveal melanoma (UM) and to assess the effect of tumor thickness and location on final outcomes. METHODS: Medical records of 234 patients undergoing Ru-106 plaque radiotherapy for UM were reviewed, and the visual outcome, globe preservation, and patient survival were evaluated. The results of 2 groups were compared: 1. between thin (small and medium-sized, thickness < 7 mm, 148 eyes [63.2%]) and thick (thickness ≥ 7 mm, 86 eyes [36.8%]) tumors, and 2. between large (largest basal diameter [LBD] > 12 mm, 109 eyes [46.6%]) and medium/small (LBD ≤ 12 mm, 125 eyes [53.4%]). In addition, a comparison of the juxtapapillary location in 46 eyes (19.7%) versus tumors arising elsewhere and between tumors with and without ciliary involvement in 48 eyes (21.5%) were done. RESULTS: The patients were followed for a median of 54.2 months (range: 6-194.5 months). After adjusting for baseline visual acuity (VA), there was no significant association between final VA and different dimension and tumor location groups. Final globe preservation was 91.9%, and there was no significant difference between different dimension- and ciliary body involvement groups regarding anatomical success rate. The juxtapapillary tumors had lower globe preservation (80.4% vs .94.7%, p = 0.002). The hazard ratio (HR) for enucleation in juxtapapillary tumors was HR = 6.58 (95-CI: 3.84 to 11.21). The overall metastasis rate was 6.8%, with no significant difference in juxtapapillary tumors (4.3% vs.7.4%, p = 0.455). CONCLUSIONS: Ru-106 plaque radiotherapy is an effective treatment for thick and large UM. With this type of treatment, the globe preservation rate is lower in juxtapapillary tumors, but there is no significant difference in the metastasis rate.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS OF RETINAL HYPERPERMEABILITY AND CHOROIDAL INFLAMMATION AS PREDICTORS OF SHORT-TERM FUNCTIONAL AND ANATOMICAL OUTCOMES IN EYES WITH DIABETIC MACULAR EDEMA TREATED WITH INTRAVITREAL BEVACIZUMAB.

PURPOSE: To assess spectral domain optical coherence tomography biomarkers of short-term outcomes in eyes with diabetic macular edema treated with intravitreal bevacizumab. METHODS: In a prospective interventional case series, 66 eyes with diabetic macular edema underwent 3 monthly intravitreal bevacizumab injections. Best-corrected visual acuity measurement and spectral domain optical coherence tomography were performed at baseline and at 3 months. Multivariate regression analysis was performed to investigate the baseline spectral domain optical coherence tomography parameters as predictors of functional and anatomical outcomes. RESULTS: Patients with diabetic nephropathy had greater subfoveal choroidal thickness (300.8 ± 35.54 vs. 253.0 ± 50.07 µm, P < 0.01) and were more likely to have subretinal fluid (r = 0.26, P = 0.03) at baseline. Multivariate analysis showed that the extent of external limiting membrane disruption (P = 0.03) and the extent of disorganization of retinal inner layers (P = 0.03) at baseline were predictors of best-corrected visual acuity at 3 months, whereas the extent of disorganization of retinal inner layers (P = 0.04) and duration of diabetes mellitus (P = 0.03) were predictors of central subfield thickness at 3 months. CONCLUSION: External limiting membrane disruption and disorganization of retinal inner layers, as the spectral domain optical coherence tomography biomarkers of retinal hyperpermeability, can predict short-term outcomes in diabetic macular edema eyes treated with intravitreal bevacizumab.

CHOROIDAL NEOVASCULAR MEMBRANE AFTER FINE-NEEDLE ASPIRATION BIOPSY OF VITREORETINAL LYMPHOMA.

PURPOSE: To report development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma. METHODS: Case report. A 75-year-old white woman with 14-month history of bilateral vitritis. RESULTS: Examination showed vitreous infiltration in both eyes and yellow-white subretinal pigment epithelial infiltrates temporally in the left eye. Visual acuity was 20/400 in both eyes. Transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrate in the left eye using a long 27-gauge needle attached to a 10-mL syringe revealed large B-cell lymphoma. Treatment was initiated with monthly intravitreal injections of melphalan (10 µg/0.05 mL) to both eyes. One month after first injection, visual acuity in the left eye had decreased to hand motion, and new ill-defined patches of retinal whitening were noticeable in the temporal macular area. Intravenous fluorescein angiography and optical coherence tomography angiography showed large choroidal neovascular membrane temporally at the site of previous fine-needle aspiration biopsy. Four monthly injections of intravitreal bevacizumab (1.25 mg/0.05 mL) resulted in complete regression of choroidal neovascular membrane with improvement of visual acuity to 20/100 in the left eye. CONCLUSION: This case demonstrates the rare development of choroidal neovascular membrane at the site of diagnostic transvitreal fine-needle aspiration biopsy of subretinal pigment epithelial infiltrates in an eye with vitreoretinal lymphoma.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

PURPOSE: To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). METHODS: Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. RESULTS: There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. CONCLUSION: Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

ASSOCIATION OF VITREORETINAL LYMPHOMA WITH SYSTEMIC LYMPHOMA.

PURPOSE: To determine the association between vitreoretinal lymphoma and systemic lymphoma (SL). METHODS: Single-center retrospective review of medical records. RESULTS: Of 95 patients with vitreoretinal lymphoma, 18 (19%) had associated SL (SL group) and 77 (81%) were not associated with SL (no SL group). The most common sites of SL were skin (n = 5), testis (n = 2), liver and breast (n = 2), and others (n = 9). A comparison (SL group vs. [vs.] no SL group) revealed no difference in demographic or ocular findings at initial visit. In the SL group, SL occurred before the onset of ocular symptoms in 14 (78%) patients with mean interval of 86 months (median 61, range 5-286 months) or after ocular symptoms in 4 (22%) patients with mean interval of 19 months (median 12, range 7-44 months). A comparison revealed no difference in overall frequency of pre-existing or eventual central nervous SL (50% vs. 53%, P = 0.99); however, the SL group demonstrated central nervous SL more often after onset of ocular symptoms (78% vs. 17%, P = 0.001). A comparison found no difference in treatment methods, response of vitreoretinal lymphoma to treatment, final visual outcome, or death rate. CONCLUSION: We found 19% of patients with vitreoretinal lymphoma demonstrate related SL, and there was no difference in demographics, clinical features, or response to treatment, compared to those not associated with SL.

Optical coherence tomography angiography analysis of the retina in patients recovered from COVID-19: a case-control study.

OBJECTIVE: To quantify the density of the macular microvasculature and the area of the foveal avascular zone (FAZ) in patients recovered from coronavirus disease 2019 (COVID-19) using optical coherence tomography angiography (OCTA) analysis. METHODS: In a comparative cross-sectional, observational study, patients recovered from COVID-19 were included in this study. All included subjects exhibited a reverse transcription-polymerase chain reaction-confirmed diagnosis of COVID-19. Spectral domain macular OCTA was performed at least 2 weeks after recovery from systemic COVID-19. Vessel density (VD) of the superficial (SCP) and deep retinal capillary plexus (DCP) and the area of the FAZ were measured in COVID-19 recovered patients versus age-matched normal controls. RESULTS: Thirty-one recovered COVID-19 patients and 23 healthy normal controls were studied. Mean quality scan index was 7.64 ± 0.66 in the COVID cases and 8.34 ± 0.71 in the normal controls (p = 0.001). Mean SCP VD and DCP VD of the COVID cohort were significantly lower than the SCP VD and DCP VD of the control group in the foveal and parafoveal regions. FAZ area was greater in the COVID cohort, but this difference was not statistically significant. In addition, in the COVID cohort, VD of the SCP was lower in patients with a history of COVID-19 hospitalization versus those without such a history, but this did not reach statistical significance. CONCLUSIONS: Patients recovered from COVID-19 displayed alterations in the retinal microvasculature, including a significantly lower VD in the SCP and DCP. Patients with coronavirus infection may be at risk of retinal vascular complications.

Photodynamic Therapy in Ocular Oncology.

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.

Anterior Uveitis with Posterior Synechia and Iris Atrophy Following Implantation of a Phakic Intraocular Lens.

PURPOSE: To describe a case with acute postoperative uveitis, posterior synechia and iris atrophy following iris-claw phakic intraocular lens (pIOL) implantation. METHODS: A case report. RESULTS: A 26-year-old man with high myopia had implantation of a -14.0 diopter, foldable, iris-claw Artiflex (model 401) anterior chamber pIOL (Ophtec B.V.) in both eyes. On the third postoperative day, the patient had significant postoperative inflammation in the left eye and received topical steroids and mydriatic eye drops. On the fifth postoperative day, the right eye had a round pupil and centered pIOL, but the left eye had an atrophic iris and dilated pupil with significant posterior synechias over the inferior half of the pupil. Despite intensive topical steroid application, the synechias remained one year after surgery. CONCLUSION: Severe uveitis with posterior synechia can occur after iris-claw pIOL implantation. We hypothesized that excessive iris tissue enclavation in the pIOLs haptics and large iridotomies may be an associated factor.

Wide-Field (15â€Š× 9 mm) Swept-Source Optical Coherence Tomography Angiography Following Plaque Radiotherapy of Choroidal Melanoma: An Analysis of 105 eyes.

PURPOSE: The aim of this study was to evaluate retinal microvascular abnormalities following plaque radiotherapy of choroidal melanoma (CM) using wide-field swept-source optical coherence tomography angiography (OCTA). DESIGN: Single-centre retrospective review. METHODS: Retrospective case series of 105 CM patients treated with I-125 plaque radiotherapy and imaged with wide-field (15 × 9 mm) SS-OCTA from March 2018 to August 2018 at the Ocular Oncology Service, Wills Eye Hospital (Philadelphia, PA). RESULTS: At mean follow-up of 49 months (range 4-297) after plaque radiotherapy, there were 52 eyes (50%) with clinically evident radiation retinopathy (CERR) and 53 eyes (50%) without CERR. Comparison (CERR vs controls) revealed foveal avascular zone enlargement (1.7 vs 0.23 mm, P = 0.03) and reduction of capillary vascular density (CVD) in the superficial and deep plexus in the total wide-field (43% vs 47%, P < 0.001, and 46% vs 48%, P = 0.001, respectively), peripapillary region (66% vs 77%, P < 0.001, and 66% vs 72%, P = 0.001, respectively), and papillomacular bundle (60% vs 68%, P < 0.001, and 61% vs 64%, P = 0.03, respectively). Comparison (no CERR vs controls) revealed nonsignificant foveal avascular zone enlargement (1.20 vs 0.23 mm, P = 0.16) and reduction of CVD in the superficial plexus (46% vs 47%, P = 0.008), and not the deep plexus (48% vs 48%, P = 0.42) of the total wide-field. Comparison of irradiated eyes (CERR vs no CERR) showed reduction of CVD in the superficial and deep plexus of the total wide-field (43% vs 46%, P < 0.006, and 46% vs 48% P < 0.02, respectively), peripapillary region (66% vs 74%, P < 0.001, and 66% vs 72% P < 0.01, respectively), and superficial plexus in the papillomacular bundle (60% vs 65%, P = 0.03). CONCLUSIONS: Following plaque radiotherapy for choroidal melanoma, wide-field swept-source optical coherence tomography angiography demonstrates retinal microvascular abnormalities in the CVD in eyes with and without CERR. These findings are important in early detection and monitoring of radiation retinopathy.

Impact of uveal melanoma thickness on post-plaque radiotherapy outcomes in the prophylactic anti-vascular endothelial growth factor era in 1131 patients.

IMPORTANCE: The impact of tumour thickness on radiation complications following plaque radiotherapy for uveal melanoma in the anti-vascular endothelial growth factor (VEGF) era remains unknown. BACKGROUND: To evaluate treatment outcomes following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma based on initial tumour thickness. DESIGN: This was a retrospective, interventional case series. PARTICIPANTS: Patients with uveal melanoma were included in this study. METHODS: A review of medical records was conducted of patients with uveal melanoma treated with plaque radiotherapy and prophylactic intravitreal bevacizumab from 7 July 2000 to 2 November 2018. MAIN OUTCOMES MEASURES: Radiation-related outcomes of cystoid macular oedema (CME), radiation maculopathy, papillopathy, retinopathy, iris neovascularization (NVI) and neovascular glaucoma (NVG) were compared based on tumour thickness (small [<3.0 mm] vs medium [3.1-8.0 mm] vs large [>8.0 mm]). RESULTS: Of 1131 eyes, 341 (30%) had small, 633 (56%) medium and 157 (14%) large melanoma. Comparison (small vs medium vs large) at 4 years following radiotherapy revealed large melanoma with greater Kaplan-Meier estimated risk of CME (37% vs 37% vs 63%, P < .001), earlier onset of CME (33 vs 26 vs 19 months, P < .001) and greater development of NVI (<1% vs 2% vs 13%, P < .001) and NVG (1% vs 2% vs 12%, P < .001). Radiation-induced maculopathy, papillopathy and retinopathy were not associated with tumour thickness. CONCLUSIONS AND RELEVANCE: Compared with small and medium uveal melanoma, large uveal melanoma demonstrated greater 48-month risk for CME, shorter time to CME onset and greater development of NVI and NVG following plaque radiotherapy and prophylactic intravitreal bevacizumab.

Prophylactic Intravitreal Bevacizumab After Plaque Radiotherapy for Uveal Melanoma: Analysis of Visual Acuity, Tumor Response, and Radiation Complications in 1131 Eyes Based on Patient Age.

PURPOSE: The aim of this study was to determine the impact of age on radiation complications after plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma. DESIGN: Retrospective cohort study. METHODS: Retrospective single-center study of plaque-irradiated uveal melanoma with prophylactic intravitreal bevacizumab at 4-month intervals from July 2000 to January 2018. RESULTS: Of 1131 eyes in 1131 patients, age was <50 years (n = 231), 50 to 70 years (n = 657), or >70 years (n = 243). Comparison by age category (<50 vs 50-70 vs >70 years) revealed the oldest group presenting with greatest tumor basal diameter (11.3 vs 11.3 vs 12.1 mm, P = 0.03) and worst visual acuity (20/40 vs 20/40 vs 20/50, P = 0.02). After plaque (mean follow-up 40 vs 42 vs 32 months, P < 0.001), radiation complications were most common in the youngest age group, including maculopathy (48% vs 39% vs 28%, P < 0.001), extramacular retinopathy (30% vs 25% vs 16%, P = 0.002), and papillopathy (21% vs 18% vs 12%, P = 0.03). The youngest age group had the highest Kaplan-Meier estimated 48-month cumulative probability for radiation maculopathy (62% vs 46% vs 47%, P = 0.001), extramacular retinopathy (36% vs 34% vs 29%, P = 0.03), and papillopathy (29% vs 26% vs 22%, P = 0.13). On subanalysis, the youngest age group had increased 48-month risk of developing radiation maculopathy when compared with the middle [hazard ratio (HR) = 1.5, P = 0.001] and older (HR = 1.6, P = 0.005) age groups and increased 48-month risk of developing extramacular radiation retinopathy compared with the older age group (HR = 1.5, P = 0.04). CONCLUSIONS: After plaque radiotherapy for uveal melanoma and prophylactic intravitreal bevacizumab at 4-month intervals, patients younger than 50 years old have an increased 48-month risk of radiation maculopathy.

Photodynamic Therapy for Choroidal Metastasis Tumor Control and Visual Outcomes in 58 Cases: The 2019 Burnier International Ocular Pathology Society Lecture.

PURPOSE: To determine outcomes after photodynamic therapy (PDT) for choroidal metastasis. DESIGN: Retrospective interventional case series. PARTICIPANTS: Forty-three patients with 40 eyes harboring 58 choroidal metastases. METHODS: Treatment with standard fluence PDT using verteporfin. MAIN OUTCOME MEASURES: Tumor control and visual outcomes. RESULTS: The primary cancer originated in the lung (n = 17 [39%]), breast (n = 16 [37%]), kidney (n = 3 [8%]), thyroid (n = 2 [6%]), and other sites (n = 5 [10%]). The mean patient age at entry was 61 years. Ocular symptoms included decreased visual acuity (n = 23 [53%]), visual field defect (n = 2 [5%]), floaters (n = 7 [16%]), flashes (n = 3 [7%]), and asymptomatic (n = 8 [19%]). The median entering visual acuity (Snellen equivalent) was 20/40. The median tumor diameter was 5.0 mm, and median thickness by ultrasonography was 2.0 mm. The median distance to the optic disc was 3.0 mm, and that to the foveola was 2.0 mm. Of the 43 patients, 35 maintained follow-up (40 eyes, 45 tumors), and PDT achieved tumor control with 1 session (n = 32 tumors [71%]) or 2 sessions (n = 3 tumors [7%]) and failed to achieve regression (n = 10 tumors [22%]). The 10 metastases for which treatment failed were managed further with plaque radiotherapy (n = 3), proton beam radiotherapy (n = 1), external beam radiotherapy (n = 1), systemic chemotherapy (n = 4), and observation (patient preference; n = 1). A comparison of clinical features for tumor control (PDT alone vs. PDT plus additional therapy) revealed those controlled with PDT alone were more likely to be adenocarcinoma (73% vs. 30%; P = 0.02) and those eyes were more like to achieve final visual acuity of 20/20 to 20/40 (66% vs. 30%; P = 0.03), with better median final Snellen visual acuity (20/30 vs. 20/70; not significant). Primary cancer site or ocular tumor features (size, location, color, shape, related subretinal fluid) did not impact tumor control. In the entire group of 40 eyes, visual acuity improved or remained stable in 28 (70%) and decreased in 12 (30%), related to subfoveal scar, persistent subretinal fluid, reactive exudation, radiation maculopathy, and brain metastasis. At last follow-up (mean, 20 months), of the entering 43 patients, 9 (21%) were alive and 34 (79%) had died of systemic metastasis. CONCLUSIONS: Photodynamic therapy with verteporfin is an effective outpatient method for small to medium choroidal metastatic tumors, providing tumor control in 78% of eyes and visual outcome of 20/20 to 20/40 in 66% of eyes.

Accuracy of The Cancer Genome Atlas Classification vs American Joint Committee on Cancer Classification for Prediction of Metastasis in Patients With Uveal Melanoma.

Importance: The Cancer Genome Atlas (TCGA) classification is a newly emerging method for prediction of uveal melanoma (UM)-related metastasis and death. Limited information is available regarding the accuracy of the TCGA classification for prediction of metastasis in patients with UM. Objective: To investigate the accuracy of the TCGA classification for predicting UM-related metastasis compared with the American Joint Committee on Cancer (AJCC) classification. Design, Setting, and Participants: In this retrospective cohort study, patients with UM treated with plaque radiotherapy at a tertiary referral center from October 1, 2008, to December 31, 2018, were evaluated. All patients with tumors classified according to the American Joint Committee on Cancer Staging Manual, 8th Edition, and who completed pretreatment fine-needle aspiration biopsy sampling for genetic analysis of chromosomes 3 and 8 for TCGA classification were included. Tumors were classified into 4 categories, 17 subcategories, and 4 stages using AJCC classification and further grouped into 4 classes using TCGA classification. Main Outcomes and Measures: Value of TCGA classification vs AJCC classification for predicting UM-related metastasis. Results: Of 642 included patients, 331 (51.6%) were women, and the mean (SD) age was 58.0 (13.8) years. There were 642 tumors from 642 patients classified according to both AJCC and TCGA classifications. The mean (range) follow-up time for the entire cohort was 43.7 (1.4-159.2) months. At 5 years, TCGA classification showed higher value for prediction of metastasis (4 TCGA classes: Wald statistic, 94.8; hazard ratio [HR], 2.8; 95% CI, 2.3-3.5; P < .001; 4 AJCC categories: Wald statistic, 67.5; HR, 2.6; 95% CI, 2.1-3.2; P < .001; 17 AJCC subcategories: Wald statistic, 74.3; HR, 1.3; 95% CI, 1.2-1.3; P < .001; 4 AJCC stages: Wald statistic, 67.0; HR, not applicable; P < .001). After entering TCGA and AJCC classifications into a multivariate model, TCGA classification still showed higher value for prediction of metastasis (TCGA classification: Wald statistic, 61.5; HR, 2.4; 95% CI, 1.9-2.9; P < .001; AJCC classification: Wald statistic, 35.5; HR, 1.9; 95% CI, 1.5-2.4; P < .001). Conclusions and Relevance: These results suggest that TCGA classification provides accuracy that is superior to AJCC categories, subcategories, and stages for predicting metastasis from UM. When genetic testing is available, TCGA classification can provide a more accurate way to identify patients at high risk of metastasis who might benefit from adjuvant therapy.

Clinical Features Predictive of Survival in Patients With Vitreoretinal Lymphoma: Analysis of 70 Patients at a Single Ocular Oncology Center.

PURPOSE: The aim of this study was to identify clinical factors predictive of time to central nervous system (CNS) lymphoma or death in patients with vitreoretinal lymphoma (VRL). DESIGN: Retrospective cohort study. METHODS: Patients with VRL (n = 95 patients) from Januray 1, 1984 to July 30, 2018 were identified at a single ocular oncology center and records were retrospectively reviewed. Outcomes included Kaplan-Meier estimated time to CNS lymphoma and death. RESULTS: There were 95 patients with VRL diagnosed at mean age 67 years, of which 70 patients had follow-up with the ocular oncology service. Mean time to CNS lymphoma in patients with isolated VRL was 56 months and did not differ by age, sex, bilateral ocular involvement, retinal infiltration, subretinal pigment epithelial (sub-RPE) infiltration, or treatment with prophylactic systemic chemotherapy (P > 0.05). Mean time to death was 66 months and did not differ when comparing those with CNS lymphoma diagnosed before VRL versus after VRL versus no CNS lymphoma at any time (67 vs 60 vs 64 months, P > 0.05). Presence of sub-RPE infiltration was associated with shorter mean time to death (46 vs 76 months, P = 0.04, odds ratio 1.9). Older patient age was associated with increased risk of death (odds ratio 1.0, P = 0.02). The mean time to death did not differ by sex, bilateral ocular involvement, retinal infiltration, timing of CNS or systemic lymphoma, or treatment with prophylactic systemic chemotherapy (P > 0.05). CONCLUSIONS: Patients with VRL presenting with sub-RPE infiltration could have shorter mean survival time. Further studies are required to confirm these findings and determine whether sub-RPE infiltration is associated with more aggressive CNS lymphoma.