Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials.

PURPOSE: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.gov identifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME). DESIGN: Randomized, double-masked, noninferiority phase 3 trials. PARTICIPANTS: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25-73 letters) due to center-involving DME. METHODS: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every-16-week dosing regimen was based on central subfield thickness (CST) and BCVA change. MAIN OUTCOME MEASURES: Included changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. RESULTS: In YOSEMITE and RHINE (n = 940 and 951, respectively), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimab every 8 weeks (YOSEMITE and RHINE, +10.7 letters and +10.9 letters, respectively) or T&E (+10.7 letters and +10.1 letters, respectively) were comparable with aflibercept every 8 weeks (+11.4 letters and +9.4 letters, respectively). The median number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections, respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% of patients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96. Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without an interval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average: faricimab every 8 weeks -216.0/-202.6 µm, faricimab T&E -204.5/-197.1 µm, aflibercept every 8 weeks -196.3/-185.6 µm), and more patients achieved absence of DME (CST < 325 µm; YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 87%-92%/88%-93%, faricimab T&E 78%-86%/85%-88%, aflibercept every 8 weeks 77%-81%/80%-84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92-100: faricimab every 8 weeks 59%-63%/56%-62%, faricimab T&E 43%-48%/45%-52%, aflibercept every 8 weeks 33%-38%/39%-45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, with a safety profile comparable with that of aflibercept. CONCLUSIONS: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as a personalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition to promote vascular stability and to provide durable efficacy for patients with DME. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy, Durability, and Safety of Faricimab in Patients From Asian Countries With Diabetic Macular Edema: 1-Year Subgroup Analysis of the Phase III YOSEMITE and RHINE Trials.

PURPOSE: To assess the 1-year efficacy, durability, and safety of faricimab in patients with diabetic macular edema from Asian and non-Asian countries. DESIGN: Global, multicenter, randomized, double-masked, active comparator-controlled, phase III trials. METHODS: Subgroup analysis of patients from Asian (N=144) and non-Asian (N=1747) countries randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab per personalized treatment interval (PTI), or aflibercept 2.0 mg Q8W in the YOSEMITE/RHINE (NCT03622580/NCT03622593) trials. Primary endpoint: best-corrected visual acuity (BCVA) changes from baseline at 1 year, averaged over weeks 48, 52, and 56. RESULTS: Mean BCVA change from baseline at 1 year in the Asian country subgroup was similar between arms: faricimab Q8W (n=50), +10.9 (95% CI: 8.6-13.2); faricimab PTI (n=48) +10.0 (7.7-12.4) letters; aflibercept Q8W (n=46) +9.0 (6.6-11.4) letters. BCVA gains in the non-Asian country subgroup (n=582, 584, 581) were +11.3 (10.5-12.1), +11.2 (10.5-12.0), and +10.7 (9.9-11.5) letters, respectively. At 1 year, 49% of Asian country patients in the faricimab PTI arm achieved Q16W dosing (vs. 52% non-Asian) and 78% achieved ≥Q12W dosing (vs. 72% non-Asian). Anatomic improvementswere generally greater with faricimab versus aflibercept and similar between the Asian and non-Asian country subgroups. Faricimab was well tolerated, with no new safety signals. CONCLUSIONS: Vision, durability, anatomic, and safety outcomes were generally similar between the Asian and non-Asian country subgroups, suggesting that global YOSEMITE/RHINE results may be generalized to the Asian population. These data support the benefit-risk profile of faricimab for treating Asian patients with diabetic macular edema.

Ocular findings in patients with acquired ATTRv amyloidosis following domino liver transplantation.

PURPOSE: To investigate the presence of amyloidosis-related ocular findings in patients who received domino liver transplantation from ATTRv amyloidosis donors. METHODS: We reviewed the ocular findings in patients who had previously undergone domino liver transplantation and received ophthalmologic examinations between January 2009 and March 2023. The presence of amyloidosis-related ocular findings was retrospectively assessed by two ophthalmologists. RESULTS: During the study period, a total of 7 patients with 14 eyes were examined. All patients were considered as acquired ATTRv amyloidosis. The mean age at the final visit was 64.6±8.4 years (52-75 years), and the mean time since domino liver transplantation was 167.6±76.2 months (69-257 months). The two evaluators' assessments for amyloidosis-related ocular findings were completely identical. No amyloid fibril deposition was observed in the pupil, lens, or vitreous. Five patients (10 eyes) had a Schirmer test result of 5mm or less than 5 mm, and four patients with a total of 8 eyes underwent fluorescein angiography and indocyanine green angiography, and no evidence of retinal amyloid angiopathy was found on fluorescein angiography. However, three patients with 6 eyes showed choroidal amyloid angiopathy on indocyanine green angiography. CONCLUSION: While cases of choroidal amyloid angiopathy were observed, serious amyloidosis-related ocular complications such as vitreous opacity or secondary glaucoma did not occur even in the long term after domino liver transplantation.

Long-term surgical results of trabeculectomy for secondary glaucoma in Val30Met hereditary transthyretin amyloidosis.

This study reports the long-term results of trabeculectomy (LEC) for secondary glaucoma in hereditary transthyretin (ATTRv) amyloidosis patients and its correlation with prior vitrectomy. A retrospective case series was conducted involving 31 consecutive eyes of 20 ATTRv amyloidosis patients who underwent LEC between 2007 and 2020. The mean follow-up period was 73.2 ± 37.0 months (range: 20-181 months). Postoperative intraocular pressures (IOPs) were evaluated based on the following criteria: (a) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for laser suture lysis, (b) IOP between 6 and 15 mmHg without additional glaucoma surgeries, except for laser suture lysis, and (c) IOP between 6 and 21 mmHg without additional glaucoma surgeries, except for needling and laser suture lysis. Kaplan-Meier analysis revealed survival rates after LEC of 0.52 at 36 months, 0.42 at 60 months, and 0.25 at 84 months under criterion (a); 0.49 at 36 months, 0.27 at 60 months, and 0.11 at 84 months under criterion (b); and 0.76 at 36 months, 0.71 at 60 months, and 0.65 at 84 months under criterion (c). Eyes with a history of small gauge transconjunctival vitrectomy (SGTV) exhibited a tendency towards lower survival rates, although no statistically significant difference was observed (log-rank test; p = 0.193 under criterion (a) and p = 0.0553 under criterion (b)). Our findings suggest that LEC and additional needling procedures can provide some control over IOP; however, the overall postoperative outcomes of LEC for ATTRv amyloidosis remain unsatisfactory, even in the era of SGTV with reduced conjunctival scarring.

Evaluating initial responses to brolucizumab in patients undergoing conventional anti-VEGF therapy for diabetic macular edema: a retrospective, single-center, observational study.

Our retrospective, single-center, observational study aimed to evaluate the initial responses to intravitreal injection of brolucizumab (IVBr) in patients undergoing anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). In total, 23 eyes of 20 patients with DME treated with at least one intravitreal injection of ranibizumab or aflibercept within one year and then switched to IVBr were included. Best corrected visual acuity (BCVA), central macular thickness (CMT), and macular volume (MV) on optical coherence tomography images were evaluated just before the most recent conventional anti-VEGF (ranibizumab/aflibercept) injection therapy (V1), one month after the most recent traditional anti-VEGF therapy (V2), just before the first IVBr (V3), and one month after the first IVBr (V4). BCVA, CMT, MV, and presence of intraocular inflammation (IOI) were evaluated at each visit. Anterior chamber flare values were also examined at V3 and V4. BCVA showed significant improvement at V2 (0.30 ± 0.23) than V1 (0.39 ± 0.29) and at V4 (0.34 ± 0.26) than V3 (0.48 ± 0.34) (P = 0.002, P < 0.001). However, no significant difference was observed between V2 and V4 (P = 0.257). CMT was significantly thinner at V2 (346.8 ± 90.2 µm) than V1 (495.5 ± 123.8 µm), and at V4 (322.2 ± 95.7 µm) than V3 (536.5 ± 166.0 µm) (P < 0.001, P < 0.001), but no significant difference was observed between V2 and V4 (P = 0.140). MV was significantly smaller at V2 (11.6 ± 2.0 mm3) than V1 (12.6 ± 1.9 mm3) and at V4 (11.2 ± 2.0 mm3) than V3 (12.6 ± 2.0 mm3) (P < 0.001, P < 0.001), and even significantly smaller at V4 than V2 (P = 0.009). No patient had IOI. No significant changes were observed in anterior chamber flare values between V3 and V4 (25.6 ± 14.6 vs. 24.0 ± 11.5 photon count/ms; P = 0.543). Both CMT and MV significantly reduced without any adverse events one month after switching from conventional anti-VEGF to IVBr therapy for DME, including IOI. MV was significantly lower for IVBr than anti-VEGF therapy after one month of treatment. Therefore, brolucizumab may be a viable treatment option for DME patients considering switching from conventional anti-VEGF agents for various reasons, such as poor response or inability to extend dosing intervals.

Patient referral flow between physician and ophthalmologist visits for diabetic retinopathy screening among Japanese patients with diabetes: A retrospective cross-sectional cohort study using the National Database.

AIMS/INTRODUCTION: Regular screening for diabetic retinopathy is essential. This study aimed to show the process and current situation of diabetic retinopathy screening prescribed by physicians (internists) and ophthalmologists for Japanese patients with diabetes. MATERIALS AND METHODS: This retrospective cohort study used data from the Japanese National Database of Insurance Claims between April 2016 and March 2018. Ophthalmology visits and fundus examinations are defined using specific medical procedure codes. The proportion of ophthalmology visits for patients with diabetic medication and for fundus examination among those who visited ophthalmologists was calculated in the fiscal year 2017. A modified Poisson regression analysis was carried out to identify factors associated with retinopathy screening. Similarly, quality indicators by prefectures were also calculated. RESULTS: Among 4,408,585 patients receiving diabetic medications (57.8% men, 14.1% insulin use), 47.4% visited the ophthalmology department and 96.9% of those underwent fundus examination. Regression analysis showed that female sex, older age, insulin use, medical facilities with Japan Diabetes Society certification and large medical facilities were predictors of fundus examination. By prefecture, the ophthalmology consultation rate and the fundus examination ranged 38.5-51.0% and 92.1-98.7%, respectively. CONCLUSIONS: Less than half of the patients who were prescribed antidiabetic medication by their physicians visited an ophthalmologist. However, most of the patients who visited an ophthalmologist had a fundus examination carried out. A similar tendency was noted for each prefecture. It is essential to reaffirm the necessity of recommending ophthalmologic examinations to physicians and healthcare professionals who care for patients with diabetes.

Subtype prevalence and baseline visual acuity by age in Japanese patients with neovascular age-related macular degeneration.

PURPOSE: To investigate age-specific prevalence of disease subtypes and baseline best-corrected visual acuity (BCVA) in Japanese patients with treatment-naïve neovascular age-related macular degeneration (nAMD). STUDY DESIGN: Retrospective multicenter case series. METHODS: We reviewed the records of patients with treatment-naïve nAMD who underwent initial treatment in 14 institutions in Japan sometime during the period from 2006 to 2015. In patients in whom both eyes were treated, only the eye treated first was included for analysis. The patients were stratified by age for the analysis. RESULTS: In total, 3096 eyes were included. The overall prevalence of subtypes was as follows: typical AMD, 52.6%; polypoidal choroidal vasculopathy (PCV), 42.8%; retinal angiomatous proliferation (RAP), 4.6%. The number of eyes in each age group was as follows: younger than 60 years, 199; 60s, 747; 70s, 1308; 80s, 784; 90 years or older, 58. The prevalence of typical AMD in each age group was 51.8%, 48.1%, 52.1%, 57.7%, and 55.2%, respectively. The prevalence of PCV was 46.7%, 49.1%, 44.7%, 34.4%, and 19.0%, respectively. The prevalence of RAP was 1.5%, 2.8%, 3.2%, 7.9%, and 25.9%, respectively. The prevalence of PCV decreased with age, whilst that of RAP increased. The prevalence of RAP was higher than that of PCV in patients aged 90 years or older. The mean baseline BCVA (logMAR) was 0.53. In each age group, the mean baseline BCVA was 0.35, 0.45, 0.54, 0.62, and 0.88, respectively. The mean logMAR BCVA at baseline significantly worsened with age (P < 0.001). CONCLUSION: The prevalence of nAMD subtypes differed according to age in Japanese patients. The baseline BCVA worsened with age.

Microhook ab interno trabeculotomy for secondary glaucoma in patients with hereditary transthyretin amyloidosis.

PURPOSE: To report surgical outcomes of a Microhook ab interno trabeculotomy (µLOT) procedure for glaucoma secondary to hereditary transthyretin amyloidosis (ATTRv). STUDY DESIGN: Retrospective case series. METHODS: Medical records of patients with glaucoma secondary to ATTRv with transthyretin Val30Met variant, who underwent µLOT, were retrospectively reviewed. Surgical success was categorized according to the postoperative intraocular pressures (IOPs, mmHg) as follows: (a) 6 ≤ IOP ≤ 21; (b) 6 ≤ IOP ≤ 18; and (c) 6 ≤ IOP ≤ 15, without light perception loss or additional glaucoma surgery. Secondary outcomes were glaucoma medication scores and postoperative complications. RESULTS: This study included 18 eyes (13 patients, 6 men). The mean follow-up period was 25.2±9.8 months (7-38 months). Kaplan-Meier analysis indicated success rates of (a) 1.00 at 6, 1.00 at 12, and 0.43 at 24 months; (b), 1.00 at 6, 0.93 at 12, and 0.43 at 24 months; (c) 0.94 at 6, 0.75 at 12, and 0.27 at 24 months after operation. Postoperative IOPs were significantly reduced from the baseline of 25.2±5.8 mmHg to 11.5±2.7 at 3, 12.3±4.1 at 6, and 13.8±3.9 at 12 months (Dunnett's test). Medication scores were also improved at 3 and 6 months but without a significant reduction at 12 months. There were no severe complications requiring surgical intervention except for additional glaucoma surgery. CONCLUSION: µLOT for secondary glaucoma in ATTRv is safe and effective 1 year after surgery, but the effects diminish after 2 years.

Temporal Change in Anterior Chamber Depth after Combined Vitrectomy and Cataract Surgery Using Different Sizes of Intraocular Lens.

This study aimed to investigate the temporal changes in the anterior chamber depth (ACD) and refractive prediction error (RPE) of 6 and 7 mm diameter intraocular lenses (IOLs) after cataract surgery or phacovitrectomy with or without sulfur hexafluoride (SF6) gas. We reviewed 120 eyes (120 patients) and divided them into six groups: three groups of cataract surgery alone and phacovitrectomy (with or without SF6), which were further divided according to IOL diameter (6 and 7 mm) used. We examined the ACD and IOL position using a swept-source anterior segment optical coherence tomograph at 1 day, 1 week, and 1 month postoperatively; and the RPE at 1 month postoperatively. The ACD and IOL position at postoperative day 1 in the SF6 injection groups were significantly smaller than those in the other groups (p < 0.01). At 1 week, the ACD and IOL position of the 6 mm IOL SF6 injection group was smaller than those in the other groups (p < 0.01); thus, complications such as synechia or pupillary capture should be considered in the early postopera-tive period of phacovitrectomy with SF6, especially in the 6 mm IOL. The ACD, IOL position, and RPE at 1 month did not significantly differ among the groups, regardless of the IOL diameter or SF6. In the SF6 injection groups, the ACD and IOL position gradually deepened with less gas.

Application of optical coherence tomography angiography to assess systemic severity in patients with hereditary transthyretin amyloidosis.

Hereditary transthyretin amyloidosis is an autosomal dominant form of amyloidosis caused by an abnormality in transthyretin, with various ocular manifestations. Among these, ocular amyloid angiopathy has attracted attention because of its direct link to visual impairment and its correlation with systemic severity. We hypothesized that optical coherence tomography angiographic parameters would be useful biomarkers of amyloidosis systemic severity and investigated their correlation with the systemic severity score. The primary outcome was the correlation between the systemic severity score and choriocapillaris flow deficit percentage. Secondary outcomes were the correlations between the systemic severity score and retinal optical coherence tomography angiographic parameters, including foveal avascular zone size and circularity and superficial/deep/total retinal perfusion and vessel densities. The choroidal and retinal vasculature was quantified in 36 eyes from 36 patients (age, 51.8±12.1 years; disease duration, 13.4±6.2 years). Ten eyes had a history of vitrectomy for vitreous opacity. Choriocapillaris flow deficit percentage was not significantly correlated with the systemic severity score (Spearman's rank correlation: r = 2.96×10-2, p = 0.863). Similarly, foveal avascular zone size and circularity, and superficial/deep/total retinal perfusion and vessel densities were not significantly correlated with the systemic severity score. These results may indicate that optical coherence tomography angiographic parameters are not sufficient to predict amyloidosis severity.

CHOROIDAL AMYLOID DEPOSITION: A Multicenter Study of Amyloid Lesions Identified in Late Indocyanine Green Angiography.

PURPOSE: To characterize choroidal amyloid angiopathy (CAA) using late-phase indocyanine green angiography (ICGA). METHODS: This was a multicenter retrospective observational case series on patients with transthyretin (ATTR) and AL amyloidosis who underwent ICGA. The timing of hyperfluorescence and longitudinal changes were analyzed. RESULTS: Thirty-two patients (27 with ATTR and 5 with AL) with mean age of 58.9 ± 17.4 years were included. Hyperfluorescent spots in the very late phases of ICGA, corresponding to CAA, were observed in 49 of 55 eyes (89%). The median time to maximal staining was 672 (95% confidence interval, 644-752) seconds, which was significantly later than the initial staining (503 [95% confidence interval, 447-521], P < 0.0001; Wilcoxon signed rank test). In seven patients with ATTR amyloidosis who underwent follow-up of ICGA, the CAA was stable in two patients and improved in five patients during treatment. However, 3 patients (43%) had worsening vitreous opacities in both eyes, and 4 patients (57%) developed secondary open-angle glaucoma. CONCLUSION: Most patients with amyloidosis were found to have CAA on ICGA. Up to 12.5 minutes is required for maximal ICG staining. Choroidal amyloid angiopathy improved in most patients with systemic treatment and may serve as a marker of systemic disease status.

A Case of Diagnosis of Occipital Lobe Epilepsy Complicated by Right Hemianopsia Associated with Left Occipital Lobe Cerebral Infarction.

We report a case of occipital lobe epilepsy (OLE) in a patient with occipital lobe stroke whose diagnosis was complicated by homonymous hemianopsia. An 81-year-old woman presented with a complaint of "blurred vision" on the right side and was kept under outpatient observation at the Hirabayashi Eye Clinic for homonymous lower right hemianopsia, glaucoma, and post-cataract surgery. Her past medical history included hypertension, angina pectoris, atrial fibrillation, diabetes mellitus, and left occipital lobe cerebral infarction. The corrected visual acuity and intraocular pressure were 20/16 and 12 mm Hg and 20/20 and 13 mm Hg in the right and left eye, respectively, and no change was observed in the fundus and visual field defect; hence, the patient was placed under observation. Two days later, the patient voluntarily visited a neurosurgical hospital and underwent magnetic resonance imaging. No abnormalities were detected other than the left obsolete occipital lobe stroke. Five days later, she returned to our clinic because she felt "something wobbly" on her right side. Upon examination, we suspected a transient ischemic attack based on the wobbling, closed eyelids, and loss of consciousness, and referred her to the same neurosurgical hospital. Electroencephalography (EEG) revealed spikes and waves with occipital lobe predominance, and the diagnosis of OLE was made. The patient had right-sided homonymous hemianopsia owing to left occipital lobe cerebral infarction and "blurred vision" on the same side. Thus, it is inferred that EEG is imperative for ruling out epileptic seizures.

Estimating ranibizumab injection numbers and visual acuity at 12 months based on 2-month data on branch retinal vein occlusion treatment.

Anti-vascular endothelial growth factor treatment for macular edema secondary to branch retinal vein occlusion generally provides good visual acuity (VA) improvement but may require repeated injections for years. To reduce the number of patients who suffer from avoidable VA loss caused by treatment drop-out, providing prospects of the correlation between expected vision improvement and required number of injections at the early stages of treatment may be helpful. In this post hoc analysis of the phase IV, randomized, open-label ZIPANGU study, we investigated the correlation between the data from Month 2 and Month 12 in terms of VA and required ranibizumab injection numbers. Fifty-nine patients were evaluated (ranibizumab monotherapy, 29; combination therapy, 30). In the monotherapy group, patients who received 1 and 3 injections by Month 2 received a mean total of 2.8 and 8.3 injections during the year, respectively. Data from the combination group were similar. The correlation coefficients for VA scores at Months 2 and 12 were 0.60 and 0.51 for the monotherapy and combination groups, respectively (both p < 0.01). Based on VA and injection numbers at Month 2 of treatment, physicians could provide rough prospects on patients' expected final VA and required number of injections.

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

AIMS/INTRODUCTION: In older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME. MATERIALS AND METHODS: This is a real-world clinical study including 1,552 patients with treatment-naïve center-involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55-64; C3, 65-74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years. RESULTS: From baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were -0.01 in C1, -0.06 in C2, -0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were -136.2 µm in C1, -108.8 µm in C2, -100.6 µm in C3, and -89.5 µm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti-VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001). CONCLUSIONS: Compared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real-world clinical practice.

Optical coherence tomography angiography findings before and after onset of foveal retinal neovascularization in diabetic retinopathy.

PURPOSE: To report a rare case of foveal retinal neovascularization (RNV) in a patient with diabetic retinopathy in whom the retinal microcirculation structure before and after the onset of the disease was evaluated using optical coherence tomography angiography (OCTA). OBSERVATIONS: A 54-year-old woman with diabetes mellitus was referred to our department for fundus evaluation, and was diagnosed with cataract and severe non-proliferative diabetic retinopathy in the left eye. Two years after we performed cataract surgery and pan-retinal photocoagulation in the left eye, OCTA detected a previously unidentified foveal RNV arising from the perifoveal capillary network. The vitreous retinal interface slab of OCTA and cross-sectional OCT images confirmed that this foveal RNV was an aberrant vessel invading the vitreous cavity. CONCLUSIONS AND IMPORTANCE: The findings in this case indicate that foveal RNV in diabetic retinopathy is derived from vessels outside the foveal avascular zone (FAZ), and OCTA is a useful examination for the diagnostic investigation of foveal RNV.

OCULAR ANGIOGRAPHIC FEATURES IN JAPANESE PATIENTS WITH VAL30MET HEREDITARY TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: To investigate ocular angiographic features of hereditary transthyretin amyloidosis with transthyretin Val30Met mutation (hATTR-V30M) in Japanese patients. METHODS: We retrospectively reviewed 102 eyes of 51 patients with hATTR-V30M who underwent fluorescein angiograms and indocyanine green angiograms between 2012 and 2018. Systemic severity score, fluorescein angiograms, indocyanine green angiograms, and ocular amyloidosis presentations at the final angiograms and subsequent neovascular events were evaluated. Primary outcomes were the frequency of choroidal amyloid angiopathy and retinal amyloid angiopathy (RAA). Secondary outcomes were their correlations to the systemic severity score. RESULTS: Six eyes could not be evaluated by fluorescein angiogram because of vitreous opacity. Of 96 eyes evaluated, RAA was detected in 36 (37.5%). Neovascularization was not detected. Indocyanine green angiogram indicated choroidal amyloid angiopathy in 46/51 patients (90.2%), with distinct patterns-diffuse (n = 6), focal (n = 14), and punctiform (n = 26)-based on late-phase hypercyanescence. Retinal amyloid angiopathy and choroidal amyloid angiopathy grades were associated with systemic severity (ρ = 0.57 and 0.50, respectively; both P < 0.05). At 35.4 ± 28.4 (0-96) months, iris-rubeosis was observed in one eye and vitreous hemorrhage in two. CONCLUSION: Retinal amyloid angiopathy was less common and choroidal amyloid angiopathy was frequent, and their severity correlated with the systemic severity score. The frequencies of RAA and subsequent neovascular events in this study may suggest regional differences in the ocular angiographic features of hATTR-V30M.

Treat-and-extend therapy with aflibercept for diabetic macular edema: a prospective clinical trial.

PURPOSE: To investigate the efficacy and safety of a treat-and-extend (T&E) regimen using aflibercept (Eylea) for diabetic macular edema (DME). STUDY DESIGN: Prospective, open-label, multicenter, single-arm, nonblinded clinical study. METHODS: Forty eyes of 40 patients with DME received a T&E regimen of intravitreal aflibercept injection (IAI) with the longest treatment interval set to 16 weeks and adjunct focal/grid laser for 1 year. An intent-to-treat analysis was performed using the same last-observation-carried-forward method. A per-protocol analysis was also performed for patients who completed a 1-year T&E regimen. The primary endpoints were mean changes in best-corrected visual acuity (BCVA) and central subfield macular thickness (CST) from baseline. Secondary endpoints included IAI-interval extension and resultant IAI numbers and the association between an early response to IAI and final BCVA gain at 1 year. RESULTS: Thirty-one patients (77.5%) completed the 1-year aflibercept T&E regimen. In these per-protocol participants, the mean CST improvement/reduction was 187.3 ± 145.0 µm (P < .001), but the mean BCVA gain was limited to 4.3 ± 12.2 letters (P = .782). Subanalysis revealed that eyes that gained ≥ 4 letters (median at week 12) after the initial 3 consecutive IAIs (induction phase) achieved greater vision improvement (13.8 ± 9.5 letters) than did the residual eyes (- 4.3 ± 9.2 letters) at 1 year (P < .001). Treatment intervals were extended to 12 and 16 weeks in 16.1% (5/31) and 45.2% (14/31) of the patients, respectively. The mean IAI number was 7.0 ± 1.1. CONCLUSIONS: The results of this study suggest that although the BCVA improvement might be somewhat less than that of frequent treatment, a T&E aflibercept regimen with the longest treatment interval set to 16 weeks is a realizable rational strategy for DME treatment over 1 year.