CHARACTERISTICS OF TYPE 3 NEOVASCULARIZATION LESIONS: Focus on the Incidence of Multifocal Lesions and the Distribution of Lesion Location.

PURPOSE: To evaluate the incidence of multifocal lesions and the distribution of lesion location in Type 3 neovascularization. METHODS: This retrospective, observational study included 148 eyes of 148 patients diagnosed with Type 3 neovascularization. The number of Type 3 neovascularization lesions was counted, and the incidence of multiple lesions in an eye was estimated. In addition, the distance from the fovea to the lesion and the geographic location of the lesion were estimated. Pseudodrusen incidence was compared between eyes with and without multifocal lesions. RESULTS: In total, 169 Type 3 neovascularization lesions were noted. A single lesion was noted in 130 eyes (87.8%), whereas 2 or 3 multifocal lesions were noted in the remaining 18 eyes (12.2%). The mean distance from the fovea to the lesion was 898.8 ± 324.9 µm. The distribution of lesion locations exhibited a fovea-sparing pattern. No lesions were located within 200 µm of the fovea, 20 lesions (11.8%) were located >200 and ≤500 µm away from the fovea, 89 lesions (52.7%) were located >500 and ≤1,000 µm away from the fovea, and 60 lesions (35.5%) were located >1,000 µm away from the fovea. Pseudodrusen incidence was significantly higher in eyes with multifocal lesions (P = 0.024). CONCLUSION: Two or more multifocal lesions were noted in 12.2% of eyes with Type 3 neovascularization, and pseudodrusen incidence was higher in eyes with multifocal lesions. In addition, lesion distribution exhibited a fovea-sparing pattern. These characteristics may be associated with the distinct pathophysiology of Type 3 neovascularization.

Long-term incidence and timing of reactivation in patients with type 3 neovascularization after initial treatment.

PURPOSE: The purpose of the present study was to evaluate the long-term incidence and timing of reactivation in patients with type 3 neovascularization who were treated with three monthly anti-vascular endothelial growth factor (VEGF) injections. METHODS: A total of 179 patients (179 eyes) diagnosed with type 3 neovascularization with dry macula after three monthly anti-VEGF loading injections were included in this retrospective study. After the initial treatment, patients were followed up without further injection until the first reactivation. The incidence and timing of the first reactivation after the initial treatment were recorded, and factors predictive of early reactivation (≤ 6 months after the third anti-VEGF injection) were investigated. RESULTS: During a mean follow-up of 37.5 ± 18.8 months, the first reactivation was noted in 145 patients (81.0%) at a mean of 6.6 ± 4.1 months after the third injection. In 94 eyes (64.8%), reactivation was noted 2-6 months after the third injection, while in 37 eyes (25.5%) it was noted 7-12 months after the third injection. In the remaining 14 eyes (9.7%), the reactivation was noted after this period. The incidence of early reactivation was higher in women (P = 0.014) and patients with thicker choroid (P = 0.026). CONCLUSIONS: In patients with type 3 neovascularization, almost all reactivation was noted within 15 months of the third anti-VEGF injection, suggesting the need for close follow-up and detailed examination during this period. Female patients with thick choroid should be monitored more frequently during this early period.

RECURRENCE IN PATIENTS WITH TYPE 3 NEOVASCULARIZATION (RETINAL ANGIOMATOUS PROLIFERATION) AFTER INTRAVITREAL RANIBIZUMAB.

PURPOSE: To evaluate the incidence, timing, and characteristics of recurrence in patients with Type 3 neovascularization who were initially treated with ranibizumab. METHODS: This retrospective study included 42 patients (42 eyes) who were diagnosed with Type 3 neovascularization and treated with 3 monthly injections of ranibizumab. The 12-month follow-up data of these patients were analyzed. The time of recurrence after the initial treatment was recorded. In eyes with recurrence, the association of the duration until the first recurrence and the incidence of multiple recurrences was analyzed. RESULTS: During the 12 months, recurrence was noted in 32 patients (76.2%), with 20 experiencing multiple recurrences. The first recurrence occurred (mean ± SD) 5.3 ± 1.8 months (range, 2-9 months) after the third ranibizumab injection. The first recurrence was noted in 20 eyes (62.5%) at 4 months to 6 months after the third injection. A significantly higher incidence of multiple recurrences was noted in patients who experienced their first recurrence less than 6 months after the third injection (13 of 16 eyes, 83.3%) compared with patients who had their first recurrence 6 or more months after the third injection (5 of 14 eyes, 35.7%) (P = 0.011). CONCLUSION: Recurrence did not occur in 23.8% of the patients with Type 3 neovascularization who were initially treated with 3 monthly ranibizumab injections. Close follow-up examination may be needed 4 months to 6 months after the third ranibizumab injection. The close follow-up or continuous injection may also be required for patients with early first recurrences.

Risk of Retinal Neovascularization in Cases of Uveitis.

PURPOSE: To evaluate the risk of and risk factors for retinal neovascularization (NV) in cases of uveitis. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with uveitis at 4 US academic ocular inflammation subspecialty practices. METHODS: Data were ascertained by standardized chart review. Prevalence data analysis used logistic regression. Incidence data analysis used survival analysis with time-updated covariates where appropriate. MAIN OUTCOME MEASURES: Prevalence and incidence of NV. RESULTS: Among uveitic eyes of 8931 patients presenting for initial evaluation, 106 of 13,810 eyes had NV (prevalence = 0.77%, 95% confidence interval [CI], 0.60-0.90). Eighty-eight more eyes developed NV over 26,465 eye-years (incidence, 0.33%/eye-year; 95% CI, 0.27-0.41). Factors associated with incident NV include age <35 years compared with >35 years (adjusted hazard ratio [aHR], 2.4; 95% CI, 1.5-3.9), current cigarette smoking (aHR, 1.9; 95% CI, 1.1-3.4), and systemic lupus erythematosus (aHR, 3.5, 95% CI, 1.1-11). Recent diagnosis of uveitis was associated with an increased incidence of NV (compared with patients diagnosed >5 years ago, aHR, 2.4 [95% CI, 1.1-5.0] and aHR, 2.6 [95% CI, 1.2-6.0] for diagnosis within <1 year vs. 1-5 years, respectively). Compared with anterior uveitis, intermediate uveitis (aHR, 3.1; 95% CI, 1.5-6.6), posterior uveitis (aHR, 5.2; 95% CI, 2.5-11), and panuveitis (aHR, 4.3; 95% CI, 2.0-9.3) were associated with a similar degree of increased NV incidence. Active (aHR, 2.1, 95% CI, 1.2-3.7) and slightly active (aHR, 2.4, 95% CI, 1.3-4.4) inflammation were associated with an increased incidence of NV compared with inactive inflammation. Neovascularization incidence also was increased with retinal vascular occlusions (aHR, 10, 95% CI, 3.0-33), retinal vascular sheathing (aHR, 2.6, 95% CI, 1.4-4.9), and exudative retinal detachment (aHR, 4.1, 95% CI, 1.3-13). Diabetes mellitus was associated with a somewhat increased incidence of retinal NV (aHR, 2.3, 95% CI, 1.1-4.9), and systemic hypertension (aHR 1.5, 95% CI, 0.89-2.4) was associated with nonsignificantly increased NV incidence. Results were similar in sensitivity analyses excluding the small minority of patients with diabetes mellitus. CONCLUSIONS: Retinal NV is a rare complication of uveitis, which occurs more frequently in younger patients, smokers, and those with intermediate/posterior/panuveitis, systemic vasculopathy, retinal vascular disease, or active inflammation. Inflammation and retinal NV likely are linked; additional studies are needed to further elucidate this connection.

Characteristics of Neovascular Age-Related Macular Degeneration in Brazilian Patients.

PURPOSE: To report features of neovascular age-related macular degeneration (AMD) in Brazilian patients. PROCEDURES: Data were prospectively collected from patients diagnosed with neovascular AMD. Eyes were classified as having typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), or retinal angiomatous proliferation (RAP). RESULTS: In total, 265 eyes of 207 patients of predominantly Caucasian ancestry were included; 166 (62.6%) eyes had typical neovascular AMD, 65 (24.5%) eyes had PCV, and 34 (12.8%) eyes had RAP. RAP demonstrated a higher percentage of bilateral cases (p = 0.015). The mean foveal subfield thickness was significantly lower in eyes with PCV (p < 0.001). Cases with typical neovascular AMD had a higher percentage of predominantly classic and minimally classic lesions on fluorescein angiography (FA; p = 0.005). CONCLUSIONS: In Brazilian patients, PCV and RAP represented 24.5 and 12.8% of neovascular AMD cases. Neovascular AMD subtypes differ in relation to clinical features, mean foveal subfield thickness and FA presentation.

Incidence and characteristics of neovascularization in fellow eyes of Japanese patients with unilateral retinal angiomatous proliferation.

PURPOSE: To describe the incidence and characteristics of neovascularization in fellow eyes of Japanese patients with unilateral retinal angiomatous proliferation (RAP). METHODS: We retrospectively studied patients with unilateral RAP in one center between 2003 and 2010. The minimal follow-up time was 2 years. The prevalence rates of soft drusen and reticular pseudodrusen in the fellow eyes at the first visit were examined in color fundus photographs and optical coherence tomography images. Stepwise analysis was performed to identify a correlation between the incidence of RAP in the fellow eyes and age, gender, follow-up time, soft drusen, and reticular pseudodrusen. RESULTS: Twenty eyes were included in this study. The mean follow-up time was 49 months (range, 24-108 months). At the first visit, soft drusen was seen in 19 eyes (95%) and reticular pseudodrusen in 11 eyes (55%). Neovascular age-related macular degeneration developed in 10 eyes, including RAP in 9 eyes (45%) and polypoidal choroidal vasculopathy in 1 eye (5%). Stepwise analysis showed that reticular pseudodrusen and longer follow-up time were correlated significantly (P = 0.0384 and P = 0.0341, respectively) with the incidence of RAP. CONCLUSION: Bilateral RAP developed in almost half of the eyes initially diagnosed with unilateral RAP and the incidence increased with time. Reticular pseudodrusen is a risk factor for bilateral RAP.

Local Geographic Atrophy Growth Rates Not Influenced by Close Proximity to Non-Exudative Type 1 Macular Neovascularization.

Purpose: The local growth rates of geographic atrophy (GA) adjacent to non-exudative type 1 macular neovascularization (MNV) were investigated to determine if MNV influenced GA growth. Methods: Eyes with GA and non-exudative type 1 MNV were followed for at least 1 year. Both GA and the MNV were imaged and measured using swept-source optical coherence tomography angiography (SS-OCTA) scans. Pearson correlations were computed between local growth rates of GA, which were estimated using a biophysical GA growth model, and local distances-to-MNV. Corresponding P values for the null hypothesis of no Pearson correlation were computed using a Monte Carlo approach that adjusts for spatial autocorrelations. Results: Nine eyes were included in this study. There were positive correlations (Pearson's r > 0) between distance-to-MNV and local GA growth in eight (89%) of the eyes; however, in all but one eye (11%), correlations were relatively weak and statistically nonsignificant after Bonferroni correction (corrected P > 0.05). Conclusions: SS-OCTA imaging combined with GA growth modeling and spatial statistical analysis enabled quantitative assessment of correlations between local GA growth rates and local distances-to-MNV. Our results are not consistent with non-exudative type 1 MNV having a strong inhibitory effect on local GA growth rates.

Is diabetic retinopathy related to subclinical cardiovascular disease?

OBJECTIVE: Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. This study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD. DESIGN: Population-based, cross-sectional epidemiologic study. PARTICIPANTS: Nine hundred twenty-seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis. METHODS: Diabetic retinopathy was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision-threatening DR (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI, defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or presence of carotid plaque. MAIN OUTCOME MEASURES: Associations between DR and subclinical CVD measures. RESULTS: The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15-4.73), low ABI (OR, 2.54; 95% CI, 1.08-5.99), and high ABI (OR, 12.6; 95% CI, 1.14-140.6) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, antihypertensive, and cholesterol-lowering medications. Diabetic retinopathy was not significantly associated with measures of carotid artery disease. CONCLUSIONS: In persons with diabetes without a history of clinical CVD, the presence of advanced-stage DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.

SCORE Study report #11: incidences of neovascular events in eyes with retinal vein occlusion.

PURPOSE: To investigate in The Standard Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study: (1) incidences of neovascular events and retinal capillary nonperfusion (abbreviated as "nonperfusion"), and their relationship with treatment groups; (2) neovascular incidences by nonperfusion status; and (3) pertinent baseline factors for their potential risk for neovascular events. DESIGN: Two multicenter, randomized clinical trials, 1 evaluating participants with central retinal vein occlusion (CRVO) and the other evaluating participants with branch retinal vein occlusion (BRVO). PARTICIPANTS: At 36 months, data were available for 81 participants with CRVO and 128 with BRVO. INTERVENTION: Standard care (observation or grid photocoagulation) versus 1 or 4 mg intravitreal triamcinolone. MAIN OUTCOME MEASURES: Neovascularization of the iris (NVI), neovascular glaucoma (NVG), disc or retinal neovascularization (NVD/NVE), preretinal or vitreous hemorrhage (PRH/VH), and nonperfusion. RESULTS: The cumulative 36-month incidences for CRVO and BRVO eyes, respectively, were 8.5% and 2.4% for NVI or NVG; 8.8% and 7.6% for NVD/NVE or PRH/VH. There were no differences in incidences of neovascular events or risk of nonperfusion when comparing the 3 treatment groups within diseases. For CRVO at 36 months, 16.6% of eyes with ≥5.5 disc areas of nonperfusion versus 4.0% of eyes with <5.5 disc areas of nonperfusion developed NVG (P = 0.0003); for BRVO at 36 months, 14.6% versus 2.4% developed NVD/NVE (P<0.0001). Similar results were noted for most other neovascular events. Nonperfusion was the only significant baseline factor for neovascularization in BRVO, with the risk of a neovascular event increasing with greater disc areas of nonperfusion, and the highest risk noted at ≥5.5 disc areas. CONCLUSIONS: In the SCORE Study, triamcinolone treatment was not associated with lower incidences of neovascular events or nonperfusion status compared with observation or grid photocoagulation. Cumulative 36-month incidences for most neovascular events were significantly higher for nonperfused than perfused eyes. Greater baseline disc areas of nonperfusion increased the risk of neovascularization in BRVO but not CRVO eyes, possibly owing to obscuration of retinal capillary details caused by dense hemorrhage at baseline for CRVO eyes. Increased risk of neovascularization was noted below the historical threshold of 10 disc areas of nonperfusion for retinal vein occlusion.

Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan.

The chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009-2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

Incidence and Natural History of Retinochoroidal Neovascularization in Enhanced S-Cone Syndrome.

OBJECTIVE: We examined the incidence and natural history of macular retinochoroidal neovascularization (RCN) in enhanced S-cone syndrome (ESCS). DESIGN: Retrospective case series. METHODS: This single-center study included 14 of 93 patients with ESCS who had signs of active or inactive RCN in ≥1 eye. We conducted multimodal retinal imaging, full-field electroretinography, and molecular genetic analysis of NR2E3 gene. Our main outcome measures included the cumulative incidence of RCN in ESCS, type of RCN, and mode of evolution of RCN. RESULTS: Fourteen (15.1%) of 93 patients with ESCS had RCN in ≥1 eye at 2 to 27 years of age. All 22 RCNs (21 eyes of 14 patients) were macular. Twelve of the RCNs were active with exudates/hemorrhages. Of these, 5 appeared de novo in a subretinal location, with photographic evidence of no pre-existing lesions. The latter were compatible with type 3 neovascularization or retinal angiomatous proliferation and subsequently evolved into unifocal fibrotic nodules. The remaining active lesions all had some degree of pre-existing fibrosis and remained stable. Ten inactive fibrotic nodules, identical to end-stage de novo lesions, were found and were presumed to represent healed RCNs. CONCLUSIONS: RCN, a treatable condition, may occur as early as 2 years of age and may be much more common in patients with ESCS than previously estimated. It may be the primary cause of the unifocal submacular fibrosis that is commonly observed in this condition. Additional research is needed to establish the pathogenesis of RCN in patients with ESCS and its optimal management.

Effects of the COVID-19 pandemic on neovascular age-related macular degeneration and response to delayed Anti-VEGF treatment.

OBJECTIVES: To investigate the effects of the COVID-19 pandemic on the treatment course of neovascular age-related macular degeneration (nAMD) patients who received anti-VEGF injection therapy with real-life data. METHODS: This retrospective study consisted of 116 eyes of 106 patients. Ophthalmic examination, assessment of best-corrected visual acuity (BCVA), optical coherence tomography (OCT) findings and data of last two visits before restrictions (V-2 and V-1) and the first visit (V0) after the release of national lockdown and subsequent visits (V1 and Vlast) were recorded. The lockdown period was determined by the time interval between March 11 and June 1, 2020. MAIN RESULTS: The injection interval before V-1 was significantly longer than the interval after V0 (2.56±0.9 vs. 2.14±0.8 months, P=0.02). While the median central macular thickness (CMT) was significantly increased at V0 compared to V-1 [274(132-711) vs. 238(136-628), P<0.001], the median CMT was significantly lower at V1 compared to V0 [256 (136-591) vs. 274(132-711), P=0.003]. The median BCVA was 0.67(0.1-1.1) logMAR at V-1 and significantly worsened to 0.78 (0.1-1.2) logMAR at V0 (P=0.003). Although the median BCVA improved to 0.69 logMAR (0.1-1.2) at Vlast, the difference did not reach statistical significance compared to V0 (P=0.08). CONCLUSION: Treatment delay due to the COVID-19 pandemic cause progression of nAMD and visual impairment. To plan more frequent anti-VEGF treatments and visits may be an appropriate approach until the disease stabilizes. However, it should be kept in mind that despite the improvement in OCT findings, the desired success in VA could not be achieved in the short term.

Nonexudative Macular Neovascularization - A Systematic Review of Prevalence, Natural History, and Recent Insights from OCT Angiography.

PURPOSE: To review the available literature on the prevalence, incidence, natural history, and exudative conversion rates of subclinical (treatment-naïve) nonexudative macular neovascularization (MNV) in patients with age-related macular degeneration (AMD). CLINICAL RELEVANCE: Nonexudative MNV is now known to be more prevalent in patients with AMD than initially thought and is bringing new insights into both the natural history and management of this very prevalent disease. METHODS: We conducted a literature search on PubMed, Scopus, and Web of Science, along with a manual search, from January 2014 to June 2019. We included studies that used optical coherence tomography angiography (OCTA) as a primary diagnostic tool to evaluate subclinical (treatment-naïve), nonexudative, neovascular AMD. RESULTS: Of the 258 screened articles, 12 were included. The prevalence of subclinical nonexudative neovascular AMD in the fellow eyes of patients with unilateral exudative AMD ranged from 6.25% to 27%. Although these lesions were not associated with a significant decrease in visual acuity, the presence of nonexudative MNV seems to be an important predictor of exudative disease. Incidence of exudation in the reviewed studies ranged from 20% to 80% (follow-up 6 months to 2 years). There is some evidence that nonexudative MNV may slow down the growth of adjacent geographic atrophy (GA). As long as exudation does not occur, it appears that subclinical nonexudative MNV is not responsible for the deterioration of visual function. CONCLUSIONS: Nonexudative MNV is an asymptomatic condition. Although nonexudative MNV seems to be a precursor for the formation of exudative neovascular AMD, there is evidence suggesting a protective effect in slowing the progression of GA. Early detection of nonexudative MNV before exudation develops should result in better monitoring of patients who are at high risk of conversion to exudative AMD. Though no controlled clinical trial has been performed to provide definitive recommendations, the authors of the studies included in this review agree that nonexudative lesions should not be treated until symptomatic exudation develops. Moreover, the existence of a nonexudative form of neovascular AMD would suggest that the term "neovascular AMD" should be preceded by either "exudative" or "nonexudative" when describing this neovascular stage of AMD.

Incidence and Risk for Developing Proliferative Diabetic Retinopathy after Photocoagulation for Diabetic Maculopathy.

PURPOSE: Diabetic maculopathy (DM) treated with photocoagulation may subsequently progress to proliferative diabetic retinopathy (PDR). However, there is insufficient knowledge about the incidence and risk factors for the development of PDR in patients previously treated for DM. MATERIALS AND METHODS: Survival data was used to analyze prospectively collected epidemiological and clinical data to describe the incidence and risk factors for the occurrence of PDR in all 1,235 patients photocoagulation treated for DM in a defined population from the Aarhus area, Denmark, from January 1. 1993 until December 31. 2016. RESULTS: Among 1,204 (97.5%) of the patients in whom the subsequent clinical history was known, 536 (44.5%) had died and 131 (10.9%) had received panretinal photocoagulation for PDR. The cumulative incidence of developing PDR after photocoagulation for diabetic maculopathy increased with time to reach a plateau around 13% after approximately 15 years. Earlier age at diagnosis of diabetes and higher HbA1c at the time of macular treatment were significant risk factors for the development of PDR, whereas gender, diabetes type, body mass index, known diabetes duration at the time of macular photocoagulation and blood pressure were not significant risk factors. CONCLUSIONS: In patients treated with retinal photocoagulation for DM, a tight metabolic control is accompanied with a reduced risk for subsequent progression to PDR. In the treated patients who do not develop PDR, the control interval can be gradually increased with time.

Risk factors for retinal hemorrhage after photodynamic therapy in age-related macular degeneration.

BACKGROUND: Subretinal or intraretinal hemorrhage may occur after photodynamic therapy (PDT). However, risk factors for post-PDT hemorrhage have not yet been investigated. METHODS: We reviewed the medical records of patients who had undergone PDT for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Primary outcomes were the occurrences of hemorrhages at 2 and 12 weeks after PDT. To identify the risk factors of hemorrhages after treatment, ocular and systemic factors were investigated. The secondary outcome was visual acuity. RESULTS: Ninety-two eyes from 92 patients were analyzed. New hemorrhages developed in 9 (9.8%) within 2 weeks and in 8 (8.3%) between 2 and 12 weeks after PDT. Hypertension [odds ratio (OR) 356.9, 95% confidence interval (CI) 3.7-34,487.1], minimally classic lesion (OR 53.4, 95% CI 2-1,429) and advanced age (OR 1.2, 95% CI 1-1.5) were related to hemorrhagic events within 2 weeks after PDT. A tendency toward recurrent hemorrhage was noted after repeat treatments (p < 0.05). Forty-four percent of the patients with a hemorrhagic event within 2 weeks after PDT experienced decreased vision. CONCLUSION: Hypertension, minimally classic lesion, advanced age and a previous hemorrhagic event were associated with the development of hemorrhage within 2 weeks after PDT.

Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish Ophthalmic Surveillance Unit (SOSU) study.

PURPOSE: Submacular haemorrhage (SMH) is a cause of severe visual loss in neovascular age-related macular degeneration (nAMD). The incidence is uncertain and furthermore there is no widely used classification system nor agreed best practice. The aim of this national surveillance study was to identify the incidence, presenting features and clinical course of new fovea-involving submacular haemorrhage associated with nAMD. METHODS: A questionnaire was sent monthly to every ophthalmic specialist in Scotland over a 12-month period asking them to report all newly presenting patients with acute SMH secondary to nAMD of at least two disc diameters (DDs) in greatest linear diameter. A follow-up questionnaire was sent 6 months after initial presentation. Cases related to other causes were excluded. RESULTS: Twenty-nine cases were reported giving an incidence of 5.4 per million per annum (range 2-15). The mean age was 83 years (range 66-96) and females accounted for 17/29 (59%). Fifteen of the 29 cases (52%) had a past history of AMD, of which 7 had nAMD. Nineteen of the 29 cases (66%) presented within 7 days of onset and the majority had SMH of < 11 DD (20/29, 69%). Treatment options comprised the following: observation (n = 6, 21%), anti-VEGF alone (n = 6, 21%) or vitrectomy with co-application of tissue plasminogen activator (TPA), anti-VEGF and gas (n = 17, 58%). The vitrectomy group experienced the greatest change in vision from logMAR 1.89-1.50 (p = 0.374). Four of 20 (20%) cases with 6 months follow-up suffered a re-bleed at a mean time of 96 days. CONCLUSIONS: The incidence, clinical features and course of a consecutive national cohort of patients with SMH secondary to nAMD are presented.

Two-Year Risk of Exudation in Eyes with Nonexudative Age-Related Macular Degeneration and Subclinical Neovascularization Detected with Swept Source Optical Coherence Tomography Angiography.

PURPOSE: Swept source optical coherence tomography angiography (SS-OCTA) was used to study the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with unilateral nonexudative age-related macular degeneration. DESIGN: Prospective cohort study. METHODS: Patients were imaged using 3- × 3-mm and 6- × 6-mm SS-OCTA scan patterns. MNV was detected using the outer retina to choriocapillaris en face slab. Prevalence and incidence of subclinical MNV, Kaplan-Meier cumulative estimates for the overall risk of exudation, and the association between neovascular lesion size and the risk of exudation were assessed through 2 years. RESULTS: From August 2014 through March 2018, 227 patients (154 intermediate and 73 late age-related macular degeneration eyes) underwent SS-OCTA imaging. Thirty eyes (13.2%) had subclinical MNV at first imaging and 12 eyes (8.9%) developed subclinical MNV during follow-up. Of the 191 eyes with >1 visit, 19 developed exudation. Fourteen of these eyes had pre-existing subclinical MNV. The incidence of exudation from the time of first detection of any subclinical MNV was 34.5%. The relative risk of exudation after detection of subclinical MNV was 13.6 times greater (95% confidence interval 4.9-37.7) than in the absence of subclinical MNV (P < .001). There was no significant risk of exudation based on lesion size alone (P = .91). CONCLUSIONS: By 24 months, the risk of exudation was 13.6 times greater for eyes with subclinical MNV detected by SS-OCTA compared with eyes without subclinical MNV. For eyes with subclinical MNV in the absence of symptomatic exudation, we recommend close follow-up without treatment.

Presumed ocular histoplasmosis syndrome in India.

The authors report a case series of presumed ocular histoplasmosis syndrome (POHS) from India. Patients with progressive diminution of vision and having subretinal neovascularisation (SRNVM) were evaluated thoroughly to look for signs of POHS. Three patients had features suggestive of POHS, which to the best of the authors' knowledge is the first case series reported from India. This study shows that patients with clinical features suggestive of POHS do exist in India. A thorough fundus examination of young adults with supposedly idiopathic SRNVM may help to uncover more cases of POHS in India.

Retinal angiomatous proliferation.

Retinal angiomatous proliferation (RAP) is a unique variant of neovascular age-related macular degeneration. Published studies have estimated that up to 15% of patients with neovascular age-related macular degeneration have RAP. Clinical features frequently associated with RAP include bilateral disease, presence of pigment epithelial detachments, and reticular pseudodrusen. RAP is more frequently associated with the development of retinal pigment epithelial tears and geographic atrophy that can lead to severe vision loss. Recent advances in retinal and choroidal imaging technology have furthered our understanding of RAP. Although indocyanine green angiography remains the gold standard diagnostic tool, optical coherence tomography has improved the precision by which neovascular age-related macular degeneration with RAP lesions can be diagnosed, staged, and monitored. Anti-vascular endothelial growth factor therapy is currently the first line of treatment. Other treatment options including combination of photodynamic therapy with antiangiogenic agent intravitreal injections or corticosteroids may also achieve a reasonable therapeutic outcome; however, RAP may portend a more guarded visual prognosis than typical choroidal neovascularization because of variable treatment response and dependence on the disease stage. Future basic and clinical research is needed to clarify the pathophysiology, definition and classification, optimal treatment regimen, and long-term outcome of RAP.

The United Kingdom Diabetic Retinopathy Electronic Medical Record Users Group: Report 3: Baseline Retinopathy and Clinical Features Predict Progression of Diabetic Retinopathy.

PURPOSE: To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH). DESIGN: Multicenter, national cohort study. METHODS: Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity. RESULTS: Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25-2.49, P = .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39-10.62, P = .0095). CONCLUSIONS: Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.