Efficacy of as-needed intravitreal injection compared to 3-monthly loading of anti-vascular endothelial growth factor agents for branch retinal vein occlusion.

We investigated the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents in branch retinal vein occlusion (BRVO). Databases, including PubMed, EMBASE, and the Cochrane Library, were searched on November 11, 2022. Studies comparing the pro-re-nata (PRN) regimen after the first treatment (PRN group) to three consecutive monthly injection regimens followed by the PRN regimen (3 + PRN group) were investigated. The primary outcomes were the change in best-corrected visual acuity (BCVA) and the change in central retinal thickness (CRT), with the secondary outcome being the injection frequency. Among 195 reports on anti-VEGF treatment, six comparative studies were included in this meta-analysis. The two groups had no statistically significant differences in terms of BCVA or CRT. However, the total number of injections during follow-up was significantly lower in the PRN group than in the 3 + PRN group (95% CI - 2.09 to - 0.83). The as-needed injection regimen is as effective as 3-monthly loading in terms of anatomical and functional improvement for BRVO, along with a lower treatment burden for patients and physicians.

Primary and additional treatment preference in aggressive retinopathy of prematurity and type 1 retinopathy of prematurity.

OBJECTIVE: This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP. METHODS: This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed. RESULTS: Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment. CONCLUSION: In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.

Clinical Application of Intravitreal Aflibercept Injection for Diabetic Macular Edema Comparing Two Loading Regimens.

Background and Objectives: We investigated and compared the efficacy of three and five monthly loading regimens of an intravitreal aflibercept injection (IVA) in patients with diabetic macular edema (DME). Materials and Methods: This was a retrospective study that included patients diagnosed with DME and treated with an either three or five monthly aflibercept loading regimen from July 2018 to March 2022. Information on clinical characteristics and changes in the central retinal thickness (CRT) were obtained from medical records. Results: In total, 44 eyes of 44 patients with DME treated with IVA were included in this study, with 30 eyes treated with 3-monthly loadings (three-loading group) and 14 eyes with 5-monthly loadings (five-loading group). The mean CRT significantly decreased from the baseline one month after loading in both the three-loading and five-loading groups (p < 0.001). Four cases were refractory to treatment in the three-loading group, while there were no cases of refractory DME in the five-loading group. The stability rate was significantly higher in the five-loading group at three months after loading (p = 0.033). Conclusions: Five-monthly loading regimens of IVA might be favorable for DME considering the rate of refractory cases, stable duration, and the importance of early responsiveness to IVA in DME.

Surgical Outcomes of Vitrectomy for Primary Treatment of Rhegmatogenous Retinal Detachment in Patients with Atopic Dermatitis.

PURPOSE: To investigate the clinical results of vitrectomy alone as the primary treatment for rhegmatogenous retinal detachment (RD) in patients with atopic dermatitis (AD). METHODS: The medical records of patients with AD treated for rhegmatogenous retinal detachment (RD) were retrospectively reviewed. We investigated the characteristics of retinal breaks and detachments, applied surgical methods, and results. RESULTS: Twenty eyes of 14 patients with AD who presented with rhegmatogenous RD and treated by vitrectomy were included in this analysis. Sixteen eyes (80%) were treated with vitrectomy, either alone or in combination with cataract surgery, and the retina was successfully attached to 94% of the eyes. There were four cases in which vitrectomy was combined with encircling. Reoperation was needed in half of the eyes that received vitrectomy with encircling, which presented nearly total detachment, severe proliferative vitreoretinopathy, and pseudophakia. CONCLUSIONS: Vitrectomy alone, in combination with cataract surgery, may be sufficient to treat rhegmatogenous RD in patients with AD. Additional encircling or buckling should still be considered in complicated cases.

Retinal vascular occlusions in COVID-19 infection and vaccination: a literature review.

PURPOSE: Abnormal hypercoagulability and increased thromboembolic risk are common in patients with coronavirus disease (COVID-19). COVID-19 has been suggested to cause retinal vascular damage, with several studies on COVID-19 patients with retinal vascular occlusions. We reviewed and investigated studies on retinal vascular occlusions in patients diagnosed with COVID-19 and in those vaccinated for COVID-19. METHODS: Studies that reported retinal vascular occlusion in COVID-19 patients or in vaccinated people were identified using the terms "retinal occlusion," together with "severe acute respiratory syndrome coronavirus 2", "SARS-CoV-2," "COVID-19," "coronavirus," and "vaccine," through systematic searches of PubMed and Google Scholar databases until January 7, 2022. RESULTS: Thirteen cases of retinal artery occlusion (RAO) and 14 cases of retinal vein occlusion (RVO) were identified among patients diagnosed with COVID-19. Half of the patients with RAO or RVO revealed no systemic disorders except current or past COVID-19, and ocular symptoms were the initial presentation in five cases. Among patients with RAO, most presented with central RAO at 1-14 days of COVID-19 diagnosis, with abnormal coagulation and inflammatory markers. Among those with RVO, two-thirds presented with central RVO and one-third with RVO. Eleven cases with acute macular neuroretinopathy (AMN) and/or paracentral acute middle maculopathy (PAMM) were reported among patients with COVID-19, presenting scotoma resolved spontaneously in most cases. Among the 26 cases vaccinated with either mRNA or adenoviral vector vaccines for COVID-19 and presenting retinal vascular occlusions, there were more RVO cases than RAO cases, and ocular symptoms mostly occurred within 3 weeks after vaccination. One case presented bilateral AMN and PAMM after COVID-19 vaccination. CONCLUSION: Retinal vascular occlusions might be a manifestation of COVID-19, although rare, especially in patients at risk of systemic hypercoagulability and thromboembolism. For COVID-19 vaccines, the causal relationship is controversial because there are few case reports of retinal vascular occlusions after COVID-19 vaccination.

The Association of Pachydrusen Characteristics with Choroidal Thickness and Patient's Age in Polypoidal Choroidal Vasculopathy versus Central Serous Chorioretinopathy.

We investigated the relationship between pachydrusen and choroidal thickness and age in eyes with polypoidal choroidal vasculopathy (PCV) and fellow eyes, compared to eyes with central serous chorioretinopathy (CSC). This retrospective study included 89 eyes with PCV and 146 eyes with CSC. The number, location, and shape of the pachydrusen and their association with choroidal thickness and age were analyzed. PCV eyes showed pachydrusen more frequently than eyes with CSC (52% vs. 20%, p < 0.001). Large solitary type and clustered type were more frequent in PCV eyes compared to CSC eyes (p = 0.003 and p = 0.001, respectively). Subfoveal choroidal thickness was associated with pachydrusen in eyes with PCV (odds ratio [OR] 1.006, 95% confidence interval [CI] 1.001−1.011, p = 0.027), while age was associated with pachydrusen in CSC eyes (OR 1.137, 95% CI, 1.073−1.205; p < 0.001). Pachydrusen were localized directly over the pachyvessel on optical coherence tomographic findings in approximately two thirds of PCV eyes and fellow eyes (62% and 67%, respectively). Risk factors for pachydrusen differ according to diseases. The presence of pachydrusen was associated with choroidal thickness in PCV, while the association with age was more prominent in CSC.

Changes in the Choroidal Thickness following Intravitreal Bevacizumab Injection in Chronic Central Serous Chorioretinopathy.

We evaluated the effect of intravitreal bevacizumab injection (IVB) on choroidal thickness, and studied its association with the therapeutic response in chronic central serous chorioretinopathy (CSC). The clinical features of 78 eyes with chronic CSC treated with IVB from October 2014 to June 2020 were retrospectively evaluated. Visual acuity (VA), central retinal thickness (CRT), and sub-foveal choroidal thickness (SFCT) were analyzed at baseline, 1 month following initial IVB, and the last follow-up examination. Cases showing complete recovery (resolved eyes; n = 60) were compared with those with persistent subretinal fluid (refractory eyes; n = 18). The relationship between the potential risk factors and subretinal fluid resolution was examined using logistic regression. SFCT was significantly decreased along with the CRT following IVB at the resolved state. SFCT reduction following 1 month of IVB was notably greater in the resolved eyes. The association of refractory eyes with hypertension (p = 0.003) and a thinner baseline SFCT (p = 0.024) was significant. In most of the patients with chronic CSC, VA and CRT remarkably improved following treatment with IVB. Early changes in the SFCT following IVB were associated with the therapeutic response. Patients with hypertension and a thinner baseline SFCT could be unresponsive to IVB.

Real-world treatment intensities and pathways of macular edema following retinal vein occlusion in Korea from Common Data Model in ophthalmology.

Despite many studies, optimal treatment sequences or intervals are still questionable in retinal vein occlusion (RVO) macular edema. The aim of this study was to examine the real-world treatment patterns of RVO macular edema. A retrospective analysis of the Observational Medical Outcomes Partnership Common Data Model, a distributed research network, of four large tertiary referral centers (n = 9,202,032) identified 3286 eligible. We visualized treatment pathways (prescription volume and treatment sequence) with sunburst and Sankey diagrams. We calculated the average number of intravitreal injections per patient in the first and second years to evaluate the treatment intensities. Bevacizumab was the most popular first-line drug (80.9%), followed by triamcinolone (15.1%) and dexamethasone (2.28%). Triamcinolone was the most popular drug (8.88%), followed by dexamethasone (6.08%) in patients who began treatment with anti-vascular endothelial growth factor (VEGF) agents. The average number of all intravitreal injections per person decreased in the second year compared with the first year. The average number of injections per person in the first year increased throughout the study. Bevacizumab was the most popular first-line drug and steroids were considered the most common as second-line drugs in patients first treated with anti-VEGF agents. Intensive treatment patterns may cause an increase in intravitreal injections.

Is gas/air tamponade essential for eyes with small peripheral retinal breaks without detachment during vitrectomy?

BACKGROUND: To investigate the safety of vitrectomy with laser photocoagulation in eyes with small peripheral retinal breaks without air or gas tamponade. METHODS: Among patients who underwent vitrectomy for various retinal disorders, those with small peripheral retinal breaks treated by laser photocoagulation without air or gas tamponade were included in this study. Their medical records were assessed retrospectively, and we investigated the characteristics of small peripheral retinal breaks and the incidence of postoperative retinal detachment (RD). RESULTS: Thirty-one eyes of 31 patients who presented with small peripheral retinal breaks requiring endolaser photocoagulation during vitrectomy were included in this analysis. There were two cases of iatrogenic retinal breaks that occurred during vitrectomy, while others were preexisting lesions, including retinal tears, atrophic retinal holes, and retinal holes with lattice degeneration. There were no cases of RD during the follow-up period of at least 6 months. CONCLUSIONS: Adequate laser treatment without gas or air tamponade may be sufficient during vitrectomy in cases with small peripheral retinal breaks without concurrent RD, along with complete removal of vitreoretinal traction.

Real-world incidence of endopthalmitis after intravitreal anti-VEGF injections in Korea: findings from the Common Data Model in ophthalmology.

OBJECTIVES: The aim of this study was to evaluate the real-world incidence of endophthalmitis after intravitreal anti-vascular endothelial growth factor (VEGF) injections using data from the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). METHODS: Patients with endophthalmitis that developed within 6 weeks after intravitreal anti-VEGF injections were identified in 3 large OMOP CDM databases. RESULTS: We identified 23,490 patients who received 128,123 intravitreal anti-VEGF injections. The incidence rates of endophthalmitis were 15.75 per 10,000 patients and 2.97 per 10,000 injections. The incidence rates of endophthalmitis for bevacizumab, ranibizumab, and aflibercept (per 10,000 injections) were 3.64, 1.39, and 0.76, respectively. The annual incidence has remained below 5.00 per 10,000 injections since 2011 despite the increasing number of intravitreal anti-VEGF injections. Bevacizumab presented a higher incidence rate for endophthalmitis than ranibizumab and aflibercept (incidence rate ratio, 3.17; p=0.021). CONCLUSIONS: The incidence of endophthalmitis after intravitreal anti-VEGF injections has stabilized since 2011 despite the explosive increase in anti-VEGF injections. The off-label use of bevacizumab accounted for its disproportionately high incidence of endophthalmitis. The OMOP CDM, which includes off-label uses, laboratory data, and a scalable standardized database, could provide a novel strategy to reveal real-world evidence, especially in ophthalmology.

Characterizing right-angled vessel in macular telangiectasia type 2 with structural optical coherence tomography.

We investigated the structural findings on spectral-domain optical coherence tomography (SD-OCT) related to the presence of right-angled vessels (RAV) in patients with macular telangiectasia (MacTel) type 2 with severity 3 in Korea. A retrospective multicenter cross-sectional study was conducted in six tertiary hospitals in Korea; the study included 116 MacTel type 2 eyes with severity 3. The SD-OCT findings were compared between eyes with RAV on fundus photography or fluorescein angiography and those without RAV. Logistic regression was performed to determine factors associated with the presence of RAV. Fifty eyes presented with RAV and 61 eyes without RAV. More eyes presented with only inner retinal (IR) cavities on SD-OCT among eyes without RAV than among those with RAV (P < 0.001). However, eyes with RAV presented with IR disorganization, outer retinal (OR) cavity, and ellipsoid zone (EZ) disruption more frequently than eyes without RAV did (all P < 0.001). These SD-OCT findings were significantly associated with the presence of RAV. The presence of RAV was closely related to IR disorganization, OR cavities, and EZ disruption on SD-OCT. These findings suggest an advanced phase of MacTel type 2.

Transient accumulation of subretinal fluid after half-fluence photodynamic therapy in neovascular age-related macular degeneration.

BACKGROUND: Photodynamic therapy (PDT) is known to occlude choroidal neovascularisation selectively, and there have been several reports on its adverse effects on the normal choroid and retinal pigment epithelium, resulting in decreased vision. METHODS: This retrospective interventional case series aimed to investigate the changes in visual acuity and retinal thickness in the immediate post-treatment period after half-fluence PDT, administered alone or with anti-vascular endothelial growth factor and steroids, in 29 eyes (26 patients) with neovascular age-related macular degeneration. The patients' best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography images were measured 1 day, 1 week, and 1 month post-treatment. RESULTS: Compared to the pre-treatment CFT (270.38 µm), the mean CFT was significantly increased 1 day post-treatment (387.07 µm, P = 0.001), which then started to decrease, with a mean CFT of 269.32 µm (P = 0.516) at 1 week, and of 240.66 µm (P = 0.066) at 1 month post-treatment. All CFT increases were due to the accumulation of subretinal fluid (SRF), rather than the intraretinal or subretinal pigment epithelium fluid. Relative to the pre-treatment BCVA (0.59 logMAR), the mean BCVA at 1 day (0.74 logMAR, P = 0.005) and 1 week (0.75 logMAR, P = 0.002) post-treatment was significantly deteriorated; however, it recovered to 0.62 logMAR at 1 month. The patterns of change in CFT and BCVA did not differ according to treatment modality. CONCLUSIONS: Half-fluence PDT resulted in accumulation of SRF in the immediate post-treatment period; this damage mostly recovered within a week, and the BCVA was restored within a month.

Demographic and Multimodal Imaging Features of Macular Telangiectasia Type 2: Korean Macular Telangiectasia Type 2 Study - Report No. 2.

Purpose: To investigate the demographic and multimodal imaging features of macular telangiectasia (MacTel) type 2 in Korea and their relationship with visual acuity and the clinical stage.Methods: A retrospective multicentre cross-sectional study was conducted in six tertiary hospitals in Korea and the study included 84 patients. Demographic data and imaging data of fundus photography, fundus autofluorescence (FAF), confocal blue-light reflectance (CBR), fluorescein angiography (FAG), and optical coherence tomography (OCT) were collected.Results: The Korean patients with MacTel type 2 were predominantly female (75%), and the mean logMAR visual acuity was 0.282 ± 0.280 at initial presentation. Most commonly presented signs were the loss of retinal transparency in fundus photographs (68.3%); increased autofluorescence in FAF (83.6%); increased blue reflectance involving the centre in CBR (68.0%); telangiectatic vessels in FAG (88.2%); and hyporeflective cavities in OCT (77.7%). The eyes diagnosed in the first half of the study period (2009-2014) showed a tendency to be diagnosed at more advanced severe stages than those diagnosed in the second half of the study period (2015-2019), using new severity scales based on FAG, FAF and OCT findings.Conclusion: The clinical features of MacTel type 2 in Korean patients assessed by newer imaging modalities suggest that Korean patients and the Caucasian-dominant population show similar presentations. This study showed that MacTel type 2 can be diagnosed in the earlier phase of the disease by using new imaging modalities and through better understanding of the disease.

Optical coherence tomographic features of macular telangiectasia type 2: Korean Macular Telangiectasia Type 2 Study-Report No. 1.

We analysed the imaging findings of macular telangiectasia (MacTel) type 2 in Korea using spectral domain optical coherence tomography (SD-OCT) and investigated their relationship with visual acuity and clinical stages. A retrospective multicentre cross-sectional study was conducted in six tertiary hospitals in Korea and included 129 patients. We analysed all the SD-OCT images encompassing the macular area. Hyporeflective cavities (77.7%) were the most frequently detected abnormalities in SD-OCT. Disruption of the external limiting membrane, ellipsoid zone, and interdigitation zone were found in 67 (40.4%), 87 (52.4%), and 94 eyes (56.6%), respectively. Four eyes (2.4%) had lamellar macular hole, and five eyes (3.0%) full-thickness macular hole. Neovascularisation, either subretinal or intraretinal, was found in 14 eyes (8.4%). Eyes with outer retinal hyperreflective band disruption had lower visual acuity than those without them. The presented characteristic clinical features of OCT in MacTel type 2 can not only aid in differentiating this disease from others but are also helpful for better judgement of the disease stage in daily clinical practice. Inner retinal hyporeflective cavities without outer retinal abnormalities on SD-OCT, although classified as severity scale 3, could be considered a relatively early stage in the disease process in terms of vision.

Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes.

Purpose: Proteinuria is the second most common complication after hypertension after systemic administration of bevacizumab. Therefore we aimed to analyze the effect of intravitreal bevacizumab (IVB) injection on proteinuria in patients with diabetes. Methods: Patients scheduled to receive IVB injection from May 1, 2018, to December 31, 2018, were prospectively enrolled. In total, 53 patients with diabetes (26 with nonproliferative diabetic retinopathy and 27 with proliferative diabetic retinopathy) and 37 patients without diabetes were included. Urine tests were performed within 1 month of and 7 ± 1 days after IVB injection. Urinary protein, creatinine, and albumin concentrations were quantitatively measured, and urinary protein-to-creatinine ratio and urinary albumin-to-creatinine ratio (UACR) were calculated from these data before and after IVB injection. Results: The mean urinary microalbumin concentrations and urinary protein-to-creatinine ratio were significantly higher in patients with diabetes, both before and after IVB injection. There were no differences between patients with nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. About 80% of patients with diabetes showed improved albuminuria or at least no harmful effect in terms of albuminuria. Patients with deteriorated baseline UACR showed more residual increase in UACR after IVB injection (P < 0.05 in all groups). Conclusions: Close monitoring of renal function after IVB might be needed in patients with diabetes according to the severity of nephropathy. Translational Relevance: Our results may provide information regarding the renal function of IVB-treated patients with diabetes.

Diabetic Retinopathy and Related Clinical Practice for People with Diabetes in Korea: A 10-Year Trend Analysis.

We performed a retrospective cohort study including people diagnosed with diabetes from 2006 to 2015 according to the Korean National Health Insurance Service-National Sample Cohort database, to analyze the changes in the prevalence, screening rate, and treatment patterns for diabetic retinopathy (DR) over 10 years. The proportion of people who underwent fundus screening for DR steadily increased over the past decade. The prevalence of DR increased from 13.4% in 2006 to 15.9% in 2015, while that of proliferative DR steadily decreased from 1.29% in 2006 to 1.16% in 2015. The proportion of patients undergoing retinal photocoagulation constantly decreased. The prevalence of DR increased over the past decade, while its severity seemed to have improved, with a decreased rate of proliferative DR and retinal photocoagulation. A higher proportion of patients underwent ophthalmic screening using fundus examination, but still less than 30% of patients with diabetes underwent comprehensive examination in 2015.

Hyperreflective foci in diabetic macular edema with serous retinal detachment: association with dyslipidemia.

AIMS: Hyperreflective foci (HF), detected in the retina of diabetic patients, suggest the presence of microglial activation and migration, while controversies still remain for the origin of HF to be precursors of hard exudates. We investigated the presence of HF and their association with dyslipidemia in serous retinal detachment (SRD)-type diabetic macular edema (DME). METHODS: Forty-two eyes in 42 patients with diabetic retinopathy (DR) and 22 eyes in 22 patients with branch retinal vascular occlusion (BRVO) showing macular edema were included in this study. The medical records and OCT findings were retrospectively reviewed in patients with SRD-type DME and compared with those with BRVO. The mean number of HF, the mean choroidal thickness, and lipid profiles were analyzed and compared between groups. RESULTS: The mean number of HF was significantly higher in DR group compared to BRVO group. Significant correlation of HF was noted with triglycerides (r = 0.523, P = 0.002). Triglycerides were significantly associated with HF by linear regression (ß = 0.012, 95% CI 0.001-0.024, P = 0.034) and remained significantly associated by multiple linear regression (ß = 0.014, 95% CI 0.003-0.025, P = 0.014). CONCLUSIONS: HF on OCT of DME patients could be indicative of activated microglia. HF are associated with dyslipidemia, especially high triglycerides, suggesting inflammatory reaction from dyslipidemia in diabetic retina.

Efficacy and safety of non-vitamin K-antagonist oral anticoagulants for retinal vascular diseases in patients with atrial fibrillation: Korean cohort study.

We investigated the prevalence of retinal vascular occlusion and intraocular bleeding and compare their risks in patients undergoing anticoagulant therapy, either with non-vitamin K-antagonist oral anticoagulants (NOAC) or warfarin. We performed a cohort study (January 2015 to April 2018) in 281,970 patients with nonvalvular atrial fibrillation (AF) using health claims in the nationwide database of the Health Insurance Review and Assessment service of Korea. A Cox-proportional hazard regression was used to calculate the hazard ratio (HR) for retinal vascular occlusion or intraocular bleeding. The HR of retinal vascular occlusion was estimated to 1.59 (95% confidence interval [CI], 1.35-1.86) for NOAC users compared to that with warfarin users. Among the various types of NOACs, all NOACs showed higher risk of retinal vascular occlusion than did warfarin. For intraocular bleeding, the HR was estimated to be 0.86 (95% CI, 0.75-0.98) for NOAC users compared with that with warfarin users. The risk of retinal vascular occlusion was higher in NOAC users than in warfarin users, while the risk of intraocular bleeding was lower with NOAC therapy. NOACs were not found to be as effective as warfarin for retinal vascular occlusion, but safe in terms of intraocular bleeding.