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.

Incidence and Clinical Features of Immunologic Rejection After Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to investigate the incidence and clinical features of immunologic rejection after deep anterior lamellar keratoplasty (DALK). METHODS: This study included 411 patients (464 eyes, median age [interquartile range; IQR] 55.8 years [36.1-69.5]) who underwent DALK at Tokyo Dental College between June 1997 and 2021. Of 411 patients, 24 (24 eyes [5.2%], 51.9 years [IQR 31.6-65.4]) developed immunologic rejection. We characterized the clinical features, risk factors associated with immunologic rejection, and prognosis. RESULTS: The interval between DALK and immunologic rejection was 14.5 (range, 5-78) months. Immunologic rejection occurred after cessation/reduction of topical steroid in 9 (47.4%) and suture removal in 4 eyes (21.1%). The postoperative duration of topical steroid use in eyes with immunologic rejection was significantly shorter (10.0 months, [IQR 6.0-14.0]) than those without immunologic rejection (28.3 [IQR 15.8-42.7], P = 0.001). Immunologic rejection manifested as stromal edema in 19 (100.0%), ciliary hyperemia in 17 (89.5%), keratic precipitates in 13 (68.4%), epithelial edema in 13 (68.4%), infiltration in 9 (47.4%), corneal opacity in 4 (21.1%), and Descemet membrane detachment in 2 eyes (10.5%). After treatment, corneal clarity was restored in 17 eyes (89.5%); however, immunologic rejection led to corneal endothelial decompensation in 2 eyes (10.5%). Endothelial cell density decreased from 1795.7 ± 722.6 to 1651.6 ± 655.6 cells/mm2 after immunologic rejection (P = 0.074). CONCLUSIONS: Post-DALK immunologic rejection was associated with specific clinical triggers such as reduction/cessation of topical steroids or suture removal.

OCT-angiography based artificial intelligence-inferred fluorescein angiography for leakage detection in retina [Invited].

Optical coherence tomography angiography (OCTA) covers most functions of fluorescein angiography (FA) when imaging the retina but lacks the ability to depict vascular leakage. Based on OCTA, we developed artificial intelligence-inferred-FA (AI-FA) to delineate leakage in eyes with diabetic retinopathy (DR). Training data of 19,648 still FA images were prepared from FA-photo and videos of 43 DR eyes. AI-FA images were generated using a convolutional neural network. AI-FA images achieved a structural similarity index of 0.91 with corresponding real FA images in DR. The AI-FA generated from OCTA correctly depicted vascular occlusion and associated leakage with enough quality, enabling precise DR diagnosis and treatment planning. A combination of OCT, OCTA, and AI-FA yields more information than real FA with reduced acquisition time without risk of allergic reactions.

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.

Corneal higher-order aberrations in corneal endothelial decompensation secondary to obstetric forceps injury.

Forceps corneal injuries during infant delivery cause Descemet membrane (DM) breaks, that cause corneal astigmatism and corneal endothelial decompensation. The aim of this study is to characterise corneal higher-order aberrations (HOAs) and corneal topographic patterns in corneal endothelial decompensation due to obstetric forceps injury. This retrospective study included 23 eyes of 21 patients (54.0 ± 9.0 years old) with forceps corneal injury, and 18 healthy controls. HOAs and coma aberrations were significantly larger in forceps injury (1.05 [0.76-1.98] µm, and 0.83 [0.58-1.69], respectively) than in healthy controls (0.10 [0.08-0.11], and 0.06 [0.05-0.07], respectively, both P < 0.0001). Patient visual acuity was positively correlated with coma aberration (rs = 0.482, P = 0.023). The most common topographic patterns were those of protrusion and regular astigmatism (both, six eyes, 26.1%), followed by asymmetric (five eyes, 21.7%), and flattening (four eyes, 17.4%). These results indicate that increased corneal HOAs are associated with decreased visual acuity in corneal endothelial decompensation with DM breaks and corneal topography exhibits various patterns in forceps injury.

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.

Role of Adrenomedullin 2/Intermedin in the Pathogenesis of Neovascular Age-Related Macular Degeneration.

Adrenomedullin 2 (AM2; also known as intermedin) is a member of the adrenomedullin (AM) peptide family. Similarly to AM, AM2 partakes in a variety of physiological activities. AM2 has been reported to exert protective effects on various organ disorders; however, its significance in the eye is unknown. We investigated the role of AM2 in ocular diseases. The receptor system of AM2 was expressed more abundantly in the choroid than in the retina. In an oxygen-induced retinopathy model, physiological and pathologic retinal angiogenesis did not differ between AM2-knockout (AM2-/-) and wild-type mice. In contrast, in laser-induced choroidal neovascularization, a model of neovascular age-related macular degeneration, AM2-/- mice had enlarged and leakier choroidal neovascularization lesions, with exacerbated subretinal fibrosis and macrophage infiltration. Contrary to this, exogenous administration of AM2 ameliorated the laser-induced choroidal neovascularization-associated pathology and suppressed gene expression associated with inflammation, fibrosis, and oxidative stress, including that of VEGF-A, VEGFR-2, CD68, CTGF, and p22-phox. The stimulation of human adult retinal pigment epithelial (ARPE) cell line 19 cells with TGF-ß2 and TNF-α induced epithelial-to-mesenchymal transition (EMT), whereas AM2 expression was also elevated. The induction of EMT was suppressed when the ARPE-19 cells were pretreated with AM2. A transcriptome analysis identified 15 genes, including mesenchyme homeobox 2 (Meox2), whose expression was significantly altered in the AM2-treated group compared with that in the control group. The expression of Meox2, a transcription factor that inhibits inflammation and fibrosis, was enhanced by AM2 treatment and attenuated by endogenous AM2 knockout in the early phase after laser irradiation. The AM2 treatment of endothelial cells inhibited endothelial to mesenchymal transition and NF-κB activation; however, this effect tended to be canceled following Meox2 gene knockdown. These results indicate that AM2 suppresses the neovascular age-related macular degeneration-related pathologies partially via the upregulation of Meox2. Thus, AM2 may be a promising therapeutic target for ocular vascular diseases.

Impact of local COVID-19 alert levels on rhegmatogenous retinal detachment.

PURPOSE: To investigate the impact of the local alert levels regarding coronavirus disease 2019 (COVID-19) on the clinical patterns of rhegmatogenous retinal detachment (RRD) in Japan. STUDY DESIGN: Retrospective, single-center, consecutive case series. METHODS: We compared two groups of RRD patients, a COVID-19 pandemic group and a control group. Based on the local alert levels in Nagano, five periods during the COVID-19 pandemic were further analyzed: epidemic 1 (state of emergency), inter-epidemic 1, epidemic 2 (second epidemic duration), inter-epidemic 2, and epidemic 3 (third epidemic duration). Patients' characteristics, including symptoms' duration before visiting our hospital, macula status, and retinal detachment (RD) recurrence rate in each period, were compared with those in a control group. RESULTS: There were 78 patients in the pandemic group and 208 in the control group. The pandemic group had a longer duration of symptoms than the control group (12.0 ± 13.5 days vs. 8.9 ± 14.7 days, P = 0.0045). During the epidemic 1 period, patients had a higher rate of macula-off RRD (71.4% vs. 48.6%) and RD recurrence (28.6% vs. 4.8%) than the control group. This period also demonstrated the highest rates compared to all other periods in the pandemic group. CONCLUSION: During the COVID-19 pandemic, RRD patients significantly delayed visiting a surgical facility. They showed a higher rate of macula-off and recurrence compared to the control group during the state of emergency than during other periods of the COVID-19 pandemic, although the difference was not statistically significant due to the small sample size.

Retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab injections for diabetic macular edema.

Purpose: To describe a case of unilateral retinal arterial occlusive vasculitis after multiple intravitreal brolucizumab (IVBr) treatments for diabetic macular edema (DME). Observations: A 68-year-old Japanese woman who had a 3-year history of insulin-dependent diabetes mellitus presented with decreased vision in the right eye (oculus dexter, OD). After two consecutive IVBr (3 mg) treatments for DME, spaced 6 weeks apart, her best corrected visual acuity improved from 20/32 to 20/28 OD, as central macular thickness (CMT) decreased from 368 µm to 253 µm on optical coherence tomography (OCT). Immediately after the 3rd IVBr, the right intraocular pressure (IOP) increased. One week later, iritis (aqueous flares: 65.0 photon count [PC]/ms) was observed, followed by localized vasculitis 2 weeks later. One month after the 3rd IVBr, extensive vasculitis and vasculitis occluding retinal arterioles were identified. Based on the history of IVBr use and clinical findings, intraocular inflammation (IOI) and subsequent retinal arterial occlusive vasculitis due to IVBr was diagnosed. Topical steroid administration (i.e., eye drops and subtenon injection) resulted in improvement of IOI after 3 months. She subsequently underwent two intravitreal aflibercept injections for DME and panretinal photocoagulation (PRP) to prevent the development of proliferative changes due to diabetic retinopathy. One year after the diagnosis of retinal arterial occlusive vasculitis, the patient had slight loss of vision (20/50) compared to baseline, due to the progression of cataracts, and OCT angiography (OCTA) showed extensive non-perfusion area on the temporal side. However, other examination findings (IOP: 16 mmHg, aqueous flares: 30.5 PC/ms, CMT: 283 µm) were stable. Conclusions and importance: Diagnosis and treatment at a relatively early stage after the onset of IOI prevented severe visual impairment in this case. Topical betamethasone eye drops reduced anterior chamber inflammation associated with IVBr; however, vascular sheathing worsened when topical drops alone was used. Occlusive retinal vasculitis, diagnosed with fluorescein angiography (FA) and OCTA, appeared to stabilize when subtenon triamcinolone injection was added to topical steroid administration. Because the central macula was not involved, severe vision loss was prevented. It is unknown if topical steroid administration would be adequate to prevent worsening of occlusive vasculitis in other cases. Although not used in this case, oral prednisone is one treatment option that may prevent severe vision loss. However, it requires monitoring of side effects, such as elevated blood glucose levels. PRP is also an option in cases where progression of proliferative changes is a concern, as was done in this case. With these considerations in mind, it is important to diagnose brolucizumab-associated IOI and subsequent retinal arterial occlusive vasculitis in DME patients early and initiate treatment to prevent severe visual impairment. Diagnosing new IOI and subsequent retinal arterial occlusive vasculitis is more difficult in DME than in neovascular age-related macular degeneration because of the inflammatory component often associated vascular occlusions. Therefore, early IOI diagnosis and follow-up using various instruments such as laser flare cell meter, wide-field color imaging, OCT/OCTA, and FA, in addition to usual comprehensive ophthalmologic examinations, is crucial.

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.

Wide-field swept-source OCT angiography (23 × 20 mm) for detecting retinal neovascularization in eyes with proliferative diabetic retinopathy.

PURPOSE: Xephilio OCT-S1 can capture single-acquisition 23 × 20-mm wide-field swept-source optical coherence tomography angiography (SS-OCTA) images and high-resolution images using artificial intelligence. We aimed to evaluate the ability of wide-field SS-OCTA in the detection of retinal neovascularizations (NVs) in eyes with proliferative diabetic retinopathy (PDR). METHODS: This retrospective study included 64 eyes of 36 patients (age, 57 ± 10 years; 10 female, 26 male) with PDR. All patients underwent a comprehensive ophthalmological examination, including fluorescein angiography (FA), as well as fovea- and disc-centered 23 × 20-mm OCTA imaging (A-scan/B-scan, 928/807). We compared and examined the number of NV sites identified using conventional methods (merging the findings from biomicroscopy/color fundus photography, FA) and the number of NV sites identified using vitreoretinal interface and superficial retinal slabs of wide-field SS-OCTA images, including the position of NVs (nasal upper, nasal lower, temporal upper, temporal lower, or disc). RESULTS: We identified 168 NVs (32/40/45/35/16, in the abovementioned order) using the conventional method. Fovea-centered 23 × 20-mm OCTA images revealed 162 (96%) NVs (27/39/45/35/16). This method tended to miss nasal NV. In contrast, disc-centered 23 × 20-mm OCTA images identified nearly all NVs, detecting 166 (99%) NVs (32/40/44/34/16) in total. All NVs could be visualized using two wide-field OCTA images: fovea- and disc-centered. CONCLUSION: Wide-field (23 × 20 mm) SS-OCTA-especially disc-centered-using Xephilio OCT-S1 identified nearly all NVs in eyes with PDR, with a single acquisition, thereby demonstrating its potential clinical application.

Morphological Changes in the Foveal Avascular Zone after Panretinal Photocoagulation for Diabetic Retinopathy Using OCTA: A Study Focusing on Macular Ischemia.

Background and objectives: This study aimed to analyze the morphological changes in the foveal avascular zone (FAZ) after panretinal photocoagulation (PRP) in patients with diabetic retinopathy, with a particular focus on the presence or absence of comorbid diabetic macular ischemia (DMI), using optical coherence tomography angiography (OCTA). Materials and Methods: Treatment-naïve 25 eyes of 16 patients who received PRP were examined in this retrospective case series. FAZ area, perimeter, and circularity were calculated on a 3 × 3-mm en-face OCTA image before PRP (baseline) and 1 and 3 months after PRP. The patients were divided into two groups according to coexisting DMI, and each group was statistically analyzed. Results: In patients with DMI (9 eyes), FAZ area significantly decreased from the baseline to 3 months after PRP (0.86 ± 0.56 to 0.61 ± 0.31 mm2, p = 0.018), whereas FAZ perimeter and circularity remained unchanged following treatment (p = 0.569 and 0.971, respectively). In patients without DMI (16 eyes), FAZ parameters did not show statistically significant changes across the 3-month follow-up period. Conclusion: PRP significantly reduces FAZ area in patients with DMI.

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.

Correction: Sugimoto et al. Trends in the Prevalence and Progression of Diabetic Retinopathy Associated with Hyperglycemic Disorders during Pregnancy in Japan. J. Clin. Med. 2022, 11, 165.

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