Transient increase of flicker electroretinograms after combined cataract surgery and vitrectomy for idiopathic epiretinal membrane.

To determine the characteristics of the changes in the amplitude of the flicker electroretinograms (ERGs) after combined cataract surgery and vitrectomy for an idiopathic epiretinal membrane (ERM). To accomplish this, we conducted a prospective study on 20 patients. Flicker ERGs and central macular thickness (CMT) were measured before the surgery (baseline), and at 1 week, 1 month, 3 months, and 6 months postoperatively. The mean amplitude of the flicker ERGs increased significantly by 63.5% at 1 week after surgery (P < 0.001) and then gradually decreased. The amplitude at 6 months was not significantly different from the baseline amplitude. This transient increase in the flicker ERG amplitudes after ERM surgery suggests that electrophysiologic evaluations of the therapeutic effects of vitrectomy should be performed 6 months postoperatively. The mean CMT decreased significantly at 1 week postoperatively (P < 0.001) and continued to decrease progressively over six months. The relative increase of amplitude at 1 week was significantly associated with the relative decrease of CMT at 6 months, and evaluation of retinal functional changes at 1 week may be able to predict the postoperative course of the ERM.

Choroidal Osteoma With Choroidal Excavation Due to Decalcification Five Years After Photodynamic Therapy: A Case Report.

A choroidal osteoma (CO) is a relatively rare, benign tumor with ossification that develops in the choroid and undergoes enlargement and decalcification in its natural course. Photodynamic therapy (PDT) is used to induce decalcification, but there are few reports on individual cases treated with PDT. A 47-year-old Japanese man who had reduced decimal visual acuity (VA) of the right eye to 0.7 due to a CO away from the fovea was treated with PDT. The PDT resulted in a partial decalcification of CO, and the visual acuity improved to 1.0. However, the tumor slowly expanded, eventually reaching the central fovea. Decalcification and focal choroidal excavation occurred during this natural course of the disease. Although his metamorphopsia worsened, his VA was maintained at 1.0. This case highlights that a CO partially decalcified after PDT can still enlarge and decalcify over several years. These findings indicate the need for careful and continuous monitoring of eyes with a CO.

Development of acute hydrops in eye with infectious keratitis: A case report.

Purpose: To determine the characteristics of an eye that developed acute hydrops while being treated for infectious keratitis. Observation: A 35-year-old man presented with pain and blurred vision in his left eye. He had undergone cataract surgery seven years earlier and was being treated for poorly controlled atopic dermatitis. The decimal best-corrected visual acuity (BCVA) of the left eye was 0.01. Slit-lamp microscopy showed conjunctival injection, corneal opacification, and a corneal ulcer. The patient was diagnosed with infectious keratitis and was treated with topical and systemic antibiotics. During the hospitalization, the patient was noted to rub his eyes frequently and vigorously. Five days after the first visit, the cornea protruded markedly, and the stroma surrounding the ulcerated area was edematous. These findings led to a diagnosis of acute hydrops.Penetrating keratoplasty was performed to prevent corneal perforation. Histopathological study of the excised cornea showed stromal edema, infiltration of leukocytes, and a tear in Descemet's membrane. Unfortunately, the patient developed endophthalmitis the day after the surgery. The anterior chamber was irrigated with antibiotics, and antibiotics were also injected into the vitreous. The endophthalmitis gradually subsided, and two years after the surgery, the patient's decimal BCVA had improved to 0.6. Conclusion and importance: Vigorous eye rubbing in cases of infectious keratitis can induce acute hydrops, and timely surgical intervention is recommended.

Case of persistent corneal epithelial damage after cataract surgery leading to diagnosis of vitamin A deficiency.

PURPOSE: To report our findings of reduced full-field electroretinograms (ff-ERGs) and abnormal optical coherence tomographic (OCT) images in a patient with poor visual acuity after cataract surgery who was eventually diagnosed with vitamin A deficiency (VAD). METHODS: This was a clinical study of a patient who complained of blurred vision after cataract surgery. To determine the cause of the reduced vision, we recorded full-field electroretinograms (ff-ERGs) to determine the scotopic and photopic status of the retina. We also performed optical coherence tomography to assess the changes in the retinal structure. Serological tests were performed. RESULTS: A 74-year-old man presented with persistent corneal epithelial damages and reduced vision that developed after conventional cataract surgery. OCT showed an interrupted ellipsoid zone, and fundus autofluorescence (FAF) showed a severe hypofluorescence in the retina of the left eye. The scotopic ff-ERGs were severely reduced, and the photopic ff-ERGs were mildly reduced. Serological examinations revealed a vitamin A concentration < 7 IU/dL (normal, 97-316 IU/dL). Based on these findings, we diagnosed the patient with VAD and started treatment with oral vitamin A supplements. After three months, his visual acuity, ff-ERGs, and OCT findings recovered to normal levels. The amplitudes and implicit times of the RETeval flicker ERGs increased to be within the normal range, and the hypofluorescence of the left eye disappeared. The length of the photoreceptor outer segments increased after the vitamin A supplementation. CONCLUSION: Our findings indicate that the ERGs are helpful for diagnosing patients with VAD associated with persistent corneal epithelial damages.

Intraocular Inflammation Secondary to Intravitreal Brolucizumab Injection for Neovascular Age-Related Macular Degeneration in a Patient with Cognitive Impairment.

Background and Objectives: Brolucizumab (IVBr) is a recently introduced anti-vascular endothelial growth factor (anti-VEGF) which has been found to be very effective in treating neovascular age-related macular degeneration (nAMD). We reported our findings in a case of nAMD that developed intraocular inflammation (IOI) after IVBr injections. Materials and Methods: A 79-year-old man was referred to our hospital complaining of reduced vision in both eyes of one-month's duration. His decimal best-corrected visual acuity (BCVA) was 0.9 in the right eye and 1.0 in the left eye. He was diagnosed with nAMD in the left eye and was treated with intravitreal aflibercept (IVA). Despite the three-monthly IVA injections, the serous retinal pigment epithelial detachment (PED) and subretinal fluid (SRF) remained, and the VA gradually decreased to 0.1. Because of the patient being refractory to aflibercept treatment, we switched to 3-monthly IVBr injections. The BCVA gradually improved to 0.3 and optical coherence tomography (OCT) showed an absence of the serous PED and SRF. Three weeks after his third IVBr, he returned to our hospital with a complaint of reduced vision in his left eye that he first noted two weeks earlier. Our examination of the left eye showed signs of IOI mainly in the anterior chamber. The inflammation improved with topical steroids but the treatment of the IOI was delayed for two weeks. The patient was instructed that it was important to begin the treatment as soon as the symptoms of IOI developed. We then performed the Mini-Mental State Examination (MMSE), and his score indicated that he had cognitive impairment. Conclusions: We concluded that before beginning IVBr treatment in nAMD patients, a careful assessment must be made of the cognitive status of the patient.

Comparisons of Clinical Characteristics and Surgical Outcomes of Epiretinal Membrane Foveoschisis to Typical Epiretinal Membrane.

Epiretinal membrane (ERM) foveoschisis is a recently proposed clinical entity. The purpose of this study was to compare the clinical characteristics and surgical outcomes of eyes with ERM foveoschisis to those of typical ERM. The medical records of all patients with ERM-related disorders examined between 2011 and 2020 were reviewed. ERM foveoschisis was defined by the clinical criteria proposed by an international panel of experts on ERMs. The background factors, clinical characteristics, and surgical outcomes of ERM foveoschisis were compared to those of typical ERM. Forty eyes with ERM foveoschisis were compared to 333 eyes with typical ERM. The percentage of women was significantly higher in the ERM foveoschisis group (92.5%) than in the typical ERM group (48.9%, p < 0.001). The central macular thickness (CMT) was significantly thinner in the ERM foveoschisis group (340 ± 110 µm) than in the typical ERM groups (476 ± 111 µm, p < 0.01). The degree of improvement in the best-corrected visual acuity (BCVA) three months after the surgery did not differ between the two groups (p = 0.59). These results suggest that the ERM foveoschisis is more likely to occur in women and that the prognosis after surgery is comparable to typical ERM.

Anti-VEGF Treatment Strategies for 3 Subtypes of Neovascular Age-Related Macular Degeneration in a Clinical Setting: A Multicenter Cohort Study in Japan.

PURPOSE: Neovascular age-related macular degeneration (nAMD) is classified into typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This study investigated clinical features of the 3 subtypes and visual outcome associated with treatment regimens in a large cohort of patients with nAMD in a clinical setting. DESIGN: Retrospective multicenter cohort study. PARTICIPANTS: Five hundred patients with treatment-naive nAMD (268 tAMD, 200 PCV, and 32 RAP) initiated with anti-VEGF agents and followed for 1 year. METHODS: Medical records were reviewed to extract demographic data, best-corrected visual acuity at baseline and 1 year after treatment initiation, spectral-domain OCT findings, baseline fellow eye condition, systemic factors, treatment strategies, and number of intravitreal injections in the first year. MAIN OUTCOME MEASURES: Primary outcome measures were anti-VEGF treatment strategy (ranibizumab or aflibercept, anti-VEGF regimen, concomitant photodynamic therapy, drug switch), best-corrected visual acuity at 1 year, and factors associated with visual acuity. RESULTS: Patients with RAP were significantly older, were more commonly women, and had more macular lesions in fellow eye than patients with tAMD and PCV. Smoking history and diabetes prevalence were not different among the 3 subtypes. Frequencies of subretinal fluid were higher and intraretinal fluid were lower in tAMD and PCV than in RAP, whereas serous pigment epithelial detachment and subretinal hemorrhage were higher in PCV than in tAMD and RAP. Choice of anti-VEGF agents and treatment regimens did not differ among 3 subtypes. The aflibercept-to-ranibizumab ratio was approximately 7:3. The mean number of injections in 1 year was 5.3 ± 2.4 in nAMD overall, which was significantly less in pro re nata (PRN) than in treat and extend (TAE) regardless of the anti-VEGF agent. Best-corrected visual acuity improved in all 3 subtypes, although it was not significant in patients with RAP. CONCLUSIONS: This clinical study demonstrates that treatment regimens were similar in 3 subtypes and aflibercept was used in 70% of all patients. Approximately 5 injections were given in the first year regardless of the anti-VEGF agent, which was significantly less in PRN regimen than in TAE. Visual acuity improvement was observed after 1-year anti-VEGF therapy in all 3 subtypes, but was not significant in RAP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of Perfluorocarbon Use during Rhegmatogenous Retinal Detachment Surgery on Postoperative Outcomes.

INTRODUCTION: The aim of this study was to determine whether the use of perfluorocarbon liquid (PFCL) affects the rate of retinal re-attachments after an initial attachment by vitrectomy in eyes with rhegmatogenous retinal detachment (RRD). METHODS: This was a retrospective, observational, multicenter study of 3,446 eyes registered in the Japanese vitreoretinal surgery treatment information database. Of these, 2,648 eyes had undergone vitrectomy as the first surgery for RRD. The re-attachment rates after the primary vitrectomy with or without PFCL were evaluated. In addition, the significance of factors affecting the re-detachments was determined by univariate and multivariate analyses. The measured outcomes were the rates of re-attachments after the primary vitrectomy with or without the use of PFCL. RESULTS: A total of 2,362 eyes in the database were analyzed: 325 had and 2,037 did not have PFCL injected into the vitreous cavity during the vitrectomy. The rate of re-attachments was 91.5% in the PFCL group and 93.2% in the non-PFCL group (p = 0.46, χ2 test). Although there were several risk factors associated with the re-detachments in eyes without PFCL (p < 0.05, Welch's t tests, and Fisher's exact tests), they were not associated in eyes with PFCL use. However, multivariate analyses showed that there was no significant association between the use and the non-use of PFCL in the rate of re-detachments (ß = -0.08, p = 0.46). CONCLUSIONS: The use of PFCL during the initial vitrectomy for RRD does not affect the rate of re-attachments.

Factors Associated with Reclosure of Posterior Capsule Aperture by Flat Opacifications with Pearls after Nd:YAG Laser Posterior Capsulotomy.

In this retrospective case series, we investigated factors associated with posterior capsule aperture (PCA) reclosure following neodymium-yttrium aluminum garnet (Nd:YAG) laser posterior capsulotomy. The study encompassed patients who underwent cataract surgery with intraocular lens (IOL) implantation or a combined vitrectomy, cataract surgery, and IOL implantation between 2009 and 2022. PCA reclosure was observed in 22 eyes of 17 patients: 45% (10 eyes) underwent the triple procedure, and 55% (12 eyes) received cataract surgery with IOL implantation. In our clinic, 14% of patients were given IOLs with a 4% water content, while 73% (13 eyes) of those experiencing PCA reclosure had IOLs with a 4% water content. The mean interval between Nd:YAG capsulotomies was notably shorter than that between the initial cataract surgery and the first Nd:YAG laser capsulotomy. We also identified five stages of PCA reclosure progression. In conclusion, IOL water content may be linked to PCA reclosure, and the time to recurrence is shorter with each successive reclosure. Further research is needed to verify these findings and uncover additional contributing factors.

Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 µg/µL of aflibercept (Af), or 25 µg/µL of bevacizumab (Be), or 10 µg/µL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Photoreceptor function and structure in retinal degenerations caused by biallelic BEST1 mutations.

The only approved retinal gene therapy is for biallelic RPE65 mutations which cause a recessive retinopathy with a primary molecular defect located at the retinal pigment epithelium (RPE). For a distinct recessive RPE disease caused by biallelic BEST1 mutations, a pre-clinical proof-of-concept for gene therapy has been demonstrated in canine eyes. The current study was undertaken to consider potential outcome measures for a BEST1 clinical trial in patients demonstrating a classic autosomal recessive bestrophinopathy (ARB) phenotype. Spatial distribution of retinal structure showed a wide expanse of abnormalities including large intraretinal cysts, shallow serous retinal detachments, abnormalities of inner and outer segments, and an unusual prominence of the external limiting membrane. Surrounding the central macula extending from 7 to 30 deg eccentricity, outer nuclear layer was thicker than expected from a cone only retina and implied survival of many rod photoreceptors. Co-localized however, were large losses of rod sensitivity despite preserved cone sensitivities. The dissociation of rod function from rod structure observed, supports a large treatment potential in the paramacular region for biallelic bestrophinopathies.

Transient Increase of Flicker Electroretinography Amplitudes after Cataract Surgery: Association with Postoperative Inflammation.

Purpose: To determine the characteristics and cause of the increase in the amplitude of flicker electroretinography (ERG) after cataract surgery. Design: Prospective, observational clinical study. Participants: Thirty patients who underwent cataract surgery. Methods: Flicker ERGs were recorded with the RETeval system without mydriasis. The central macular thickness (CMT) was measured by OCT and the aqueous flare value (AFV) by laser flare-cell photometry. These examinations were performed before surgery and 1 day, 1 week, 1 month, 2 months, and 3 months after surgery. Linear regression analysis through the origin was used to compare the correlations between the relative changes in flicker ERG amplitudes and the changes in the CMT and AFV at different times after the surgery. Main Outcome Measures: The amplitude of flicker ERGs, CMT, and AFV. Results: The mean amplitude of flicker ERGs increased significantly by 31% at 1 week after surgery (P < 0.001); a significant increase in the amplitudes was not present at 3 months after the surgery. The mean AFV was significantly increased at 1 day after surgery (P < 0.001), and the CMT was significantly increased at 1 to 3 months after surgery (P < 0.001). The changes in flicker ERG amplitudes at 1 week after surgery were significantly associated with the changes in the CMT at 1 to 3 months after surgery (P < 0.05), and they were weakly associated with the changes in AFV at 1 day after surgery (P = 0.05). Conclusions: These results suggest that the increase in the amplitude of flicker ERGs after cataract surgery is a transient phenomenon that has a peak at 1 week after surgery. The increase of flicker ERG amplitude was associated with measures that are frequently used to evaluate postoperative inflammation. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Progress of Diabetic Macular Edema after Loading Injection of Anti-Vascular Endothelial Growth Factor Agents in Real-World Cases.

Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a retrospective, observational single-center study. DME patients with a central retinal thickness (CRT) over 350 µm received a PRN injection of anti-VEGF agents following one to three consecutive monthly loading injections (bevacizumab, ranibizumab, and aflibercept) for 6 months from January 2012 to June 2019. Results: We enrolled a total of 72 eyes for loading injections and the mean CRT improved from 434.04 ± 139.4 µm (before treatment) to 362.9 ± 125.0 µm after the loading injection. One week after injection, 36 eyes (50%) obtained a CRT of ≤350 µm. Fourteen eyes (19.4%) remained with a CRT of ≤350 µm for 6 months without additional injections. A total of 22 eyes (30.6%) had a CRT of >350 µm at 6 months. Fifteen eyes did not receive additional injections because of visual improvement. Conclusions: About 20% of DME patients can be maintained at a CRT of ≤350 µm for 6 months with only a loading injection. However, there is a tendency to delay additional injections for patients with recurrences using PRN protocol.

Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group.

PURPOSE: To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM). METHODS: This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed. RESULTS: Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001). CONCLUSIONS: The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

Posterior scleritis with choroidal detachments and periaortitis associated with IgG4-related disease: A case report.

BACKGROUND: IgG4-related diseases (IgG4-RDs) are known to disrupt the functioning of multiple organs and are usually associated with mass lesions. Periaortitis, an inflammation of the adventitia and tissues surrounding the aorta, is an example of an IgG4-RD. In ophthalmology, an enlargement of the lacrimal gland is a well-known IgG4-RD, and scleritis has also been reported to be an IgG4-RD although it is rare. We report our findings in a case with periaortitis and posterior scleritis that were present at the same time, and they responded well to systemic steroid therapy. PATIENTS CONCERNS: A 79-year-old man with dementia and Lewy bodies was referred to our hospital because of uveitis in both eyes that did not respond to topical steroid therapy. DIAGNOSIS: We found anterior scleritis in the right eye and uveitis with shallow anterior chambers in both eyes. B-mode echography showed choroidal detachments (CDs) and a T sign in the right eye. The CDs were assumed to have progressed to the posterior scleritis which then caused the severe vision reduction. The patient was referred to the Internal Medicine Department because the systemic inflammatory disease was suspected due to the high levels of C-reactive protein (CRP) and the fast erythrocyte sedimentation rate. Systemic CT scans showed periaortitis only at the lumbar region. Because of the high levels of IgG4, the patient was diagnosed with IgG4-RD. INTERVENTIONS: The patient received intravenous and oral steroid therapy. The first 125 mg of methylprednisolone (mPSL) for 3 days was intravenous, after which it was switched to oral prednisolone (PSL) therapy and the dosage was gradually reduced. OUTCOMES: The posterior scleritis and periaortitis responded well to the systemic steroid therapy. One year and a half after the onset of the disease, the patient is still taking 5 mg of PSL. CONCLUSIONS: Scleritis with multiple CDs and periaortitis were strongly suspected to be due to IgG4-RD although no definitive diagnosis was made by biopsy of the lesions. Clinicians should be aware that IgG4-RD should be considered as one of the causes of posterior scleritis.

Findings in pseudophakic eye that developed liquefied aftercataract-like substance one day after vitrectomy.

Purpose: To report our findings in a case that had an accumulation of a translucent fluid between the intraocular lens (IOL) and posterior lens capsule one day after vitrectomy for a vitreous hemorrhage. Observations: A 67-year-old woman was diagnosed with diabetes 20 years before the vitrectomy and was treated with panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) 14 years earlier. She underwent cataract surgery with an implantation of an IOL 4 years earlier. She was referred to our hospital because of a vitreous hemorrhage, and we performed uneventful vitrectomy. However, the day after the operation, a translucent liquid substance that resembled liquefied aftercataract was observed in the lens capsule bag. With time, the liquid substance became cloudy. The opacification progressed for two years after the vitrectomy, and her visual acuity decreased. We then performed neodymium: YAG (Nd: YAG) laser posterior capsulotomy, and the cloudy liquid dispersed into the vitreous and the visual acuity improved. Conclusions and importance: Our findings indicate that liquified aftercataract-like substance can form after vitrectomy in a pseudophakic eye. We suggest that the aqueous humor might flow into the space behind the IOL during or just after the vitrectomy and was trapped behind the IOL optics. Then, the proliferating lens epithelial cells might be dissolved forming the white liquid substance immediately after the surgery.

Intravitreal aflibercept for diabetic macular edema in real-world clinical practice in Japan: 24-month outcomes.

PURPOSE: To report the safety and effectiveness of intravitreal aflibercept (IVT-AFL) for diabetic macular edema (DME) in the real-world clinical practice setting in Japan. METHODS: In this prospective, multicenter, observational, post-marketing surveillance, patients with DME newly receiving IVT-AFL were enrolled. During a 24-month follow-up, the primary outcome was the occurrence of safety events. Other pre-specified endpoints were effectiveness indicators, such as best-corrected visual acuity (BCVA), central retinal thickness, and injection frequency. RESULTS: In total, 646 patients administered at least one IVT-AFL injection were included in the safety analysis. During the follow-up period, adverse events occurred in 42 patients (6.50%), whereas adverse drug reactions occurred in 12 (1.86%). In the 12 patients who had adverse drug reactions, seven events occurred in seven patients within the first month of the most recent injection. In addition, 622 patients were included in the effectiveness analysis set. The number of injections over 24 months was 3.6 ± 3.0 (mean ± standard deviation [SD]). BCVA (logarithm of the minimum angle of resolution) was 0.437 ± 0.362 (mean ± SD) (n = 622) at baseline and 0.321 ± 0.348 (n = 177) after 24 months of treatment with IVT-AFL. Central retinal thickness was 440.8 ± 134.2 µm (mean ± SD) (n = 444) at baseline and 355.5 ± 126.4 µm (n = 140) at 24 months. CONCLUSION: Routine administration of IVT-AFL for DME was not associated with new safety concerns, and BCVA outcomes were maintained over 24 months in the real-world setting. Nonetheless, patients in this real-world setting received fewer injections than those in clinical trials, suggesting that a margin for improvement exists in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02425501.

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.

Effects of suspension of anti-vascular endothelial growth factor treatment for neovascular age-related macular degeneration in clinical setting.

PURPOSE: To investigate the outcomes of a suspension of anti-vascular endothelial growth factor (anti-VEGF) treatments in the eyes with neovascular age-related macular degeneration (nAMD). METHODS: This was a retrospective study that examined eyes having no exudation for 48 weeks while undergoing intravitreal anti-VEGF injections every 12 to 16 weeks. The rate and time of recurrences, best-corrected visual acuity (BCVA), central subfield thickness (CST), number of visits, and reactivity to anti-VEGF were determined after the suspension of the anti-VEGF treatments. RESULTS: In 34 eyes of 34 patients, 17 eyes (50.0%) had a recurrence during the 24-month follow-up period. The median time of a recurrence was 10 months. The BCVA was maintained for 24 months after the suspension regardless of the development of any recurrences. In 41.7% of the eyes that resumed treatment, the duration of exudation suppression by the anti-VEGF therapy was shorter than 12 weeks during the 12 months after restarting the anti-VEGF treatments. There was a significant increase in the number of visits during the first year after beginning the suspension versus during the 1 year before the suspension (non-recurrence group; P = 0.007, recurrence group; P = 0.001). CONCLUSION: Although one-half of the eyes had a recurrence within 24 months after a suspension of anti-VEGF treatment, the BCVA was maintained after a resumption of the anti-VEGF treatments. However, the number of hospital visits increases regardless of the recurrences and the lesion stability is altered by the anti-VEGF suspension. Clinicians should explain both the advantages and disadvantages of anti-VEGF suspension to nAMD patients.