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.

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.

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.

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.

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.

TWELVE-MONTH EFFICACY OF INTRAVITREAL BEVACIZUMAB INJECTION FOR CHRONIC, ATYPICAL, OR RECURRENT CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To evaluate intravitreal bevacizumab (IVB) injection efficacy for the treatment of chronic, atypical, or recurrent central serous chorioretinopathy (CSC). METHODS: Clinical data from 77 eyes of 71 patients with chronic, atypical, or recurrent CSC treated with IVB were retrospectively analyzed. After initial 6-weekly IVB administration until no subretinal fluid remained at the fovea, additional as-needed IVBs were administered, based on optical coherence tomography findings. Best-corrected visual acuity and central retinal thickness (CRT) were analyzed at baseline and 3, 6, 9, and 12 months after initial IVB. RESULTS: The significant improvement of baseline logarithm of minimum angle of resolution best-corrected visual acuity and CRT at 3 months (both P < 0.001) was maintained throughout the 12-month follow-up period. Best-corrected visual acuity improved significantly in patients with chronic and recurrent CSC, at all time points (all P < 0.05), but not in patients with atypical CSC. The CRT reduction was significant in all subgroups during the follow-up period (all P < 0.05). Definite leakage on initial fluorescein angiography correlated with improved reduction in CRT (P = 0.039). CONCLUSION: As-needed optical coherence tomography-based IVB was effective for reducing CRT in patients with chronic, atypical, or recurrent CSC, and for vision improvement in chronic and recurrent CSC over the 1-year follow-up period.

SUBFOVEAL CHOROIDAL THICKNESS AND VASCULAR DIAMETER IN ACTIVE AND RESOLVED CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To determine the subfoveal choroidal thickness and analyze Haller's layer, Sattler's layer, and large choroidal vessel diameter in eyes with active central serous chorioretinopathy (CSC) and after resolution of CSC. METHODS: Ocular and clinical features of 32 eyes with CSC were analyzed retrospectively from October 2014 to September 2015. Subfoveal choroidal thickness and thicknesses of Haller's layer and Sattler's layer were measured in the active and resolved states. The diameter of the subfoveal choroidal hyporeflective lumen (i.e., the large choroidal vessel in Haller's layer) was also measured. RESULTS: The mean subfoveal choroidal thickness, mean thickness of Haller's layer, and mean choroidal vessel diameter were significantly less after the resolution of CSC (P < 0.001). However, the thickness of Sattler's layer did not change after the resolution of CSC (P = 0.731). There were no significant differences among the different treatment modalities. CONCLUSION: After the resolution of CSC, the subfoveal choroidal thickness and thickness of Haller's layer declined, but the reduced diameter of subfoveal choroidal vessels accounted for only about half of the total thickness changes in the choroid. These results suggest that nonvascular smooth muscle cells might play a role in the thickening of the choroid during CSC and possibly in the pathogenesis and progression of CSC.

Diabetic retinopathy is associated with diastolic dysfunction in type 2 diabetic patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: To investigate the association between diabetic retinopathy (DR) and myocardial dysfunction in patients with type 2 diabetes and dilated cardiomyopathy (dCMP). METHODS: Data were collected retrospectively from 89 patients with dCMP (46 with type 2 diabetes and 43 without diabetes) and no evidence of coronary artery disease. Echocardiographic parameters and laboratory data, including lipid profiles and fundus findings, were obtained from medical records. A left ventricular ejection fraction (LVEF) less than 40% was considered impaired systolic function, while an E/E' ratio greater than 15 was considered elevated left ventricular (LV) filling pressure. RESULTS: Baseline characteristics show that LVEF was not significantly different between patients with and without diabetes or between diabetic patients with and without DR. Among the diastolic function parameters, patients with DR exhibited higher E/E' ratios (left ventricular filling pressures) than patients without DR (23.75 ± 13.37 vs 11.71 ± 3.50, P = 0.022). Logistic regression analysis revealed that statin use lowered the risk of impaired systolic dysfunction in all patients (odds ratio (OR) 0.33, 95% confidence interval (CI) 0.12-0.92, P = 0.034) and in patients with diabetes (OR 0.273, 95% CI 0.08-0.99, P = 0.049), while the presence of DR was associated with a higher risk of elevated LV filling filling pressure in patients with diabetes (OR 18.00, 95% CI 1.50-216.62, P = 0.023). CONCLUSIONS: In conclusion, DR was associated with elevated LV filling pressure in patients with dCMP. DR may not only represent microvascular long-term complications in patients with diabetes but may also be associated with more advanced form of diastolic dysfunction among diabetic patients with cardiomyopathy.

Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy.

BACKGROUND: To investigate the effects of dyslipidemia and statin therapy on progression of diabetic retinopathy and diabetic macular edema in patients with type 2 diabetes. METHODS: The medical records of 110 patients with type 2 diabetes (70 statin users and 40 non-users) were retrospectively reviewed. The two outcome measures were progression of diabetic retinopathy by two or more steps on the early treatment diabetic retinopathy study scale and diabetic macular edema based on optical coherence tomography. Serum lipid profiles were analyzed from 6 months prior to diagnosis of diabetic macular edema. RESULTS: Diabetic retinopathy progressed in 23% of statin users and 18% of non-users (p = 0.506), but diabetic macular edema was present in 23% of statin users and 48% of non-users (p = 0.008). Statins reduced low-density lipoprotein cholesterol levels in patients with and without diabetic macular edema (p = 0.043 and p = 0.031, respectively). Among statin users, patients with diabetic macular edema had higher levels of triglycerides (p = 0.004) and lower levels of high-density lipoprotein cholesterol (p = 0.033) than those without diabetic macular edema. Logistic regression analysis showed that statin use significantly lowered the risk of diabetic macular edema [odds ratio (OR): 0.33, 95% confidence interval (CI) 0.12-0.91, p = 0.032]. Hypertriglyceridemia at 6 months prior to development of macular edema was significantly associated with central retinal thickness (OR: 1.52; 95% CI 1.14-2.02, p = 0.005). CONCLUSIONS: Lipid lowering therapy with statins protected against the development of diabetic macular edema and progression of diabetic retinopathy in patients with type 2 diabetes. Hypertriglyceridemia could be used as a surrogate marker for diabetic macular edema.

The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice.

Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC.

CHOROIDAL THICKNESS IN PATIENTS WITH CENTRAL SEROUS CHORIORETINOPATHY: Assessment of Haller and Sattler Layers.

PURPOSE: To investigate subfoveal choroidal thickness and subanalyze Haller and Sattler layers in eyes with central serous chorioretinopathy (CSC), uninvolved fellow eyes, and eyes of healthy controls using enhanced depth imaging optical coherence tomography. METHODS: Ocular findings and clinical features of 31 eyes with CSC, 24 fellow eyes and eyes of 30 healthy controls were analyzed retrospectively from October, 2014 to March, 2015. Subfoveal choroidal thickness was measured using enhanced depth imaging optical coherence tomography, and the thicknesses of Haller and Sattler layers were analyzed. RESULTS: Mean subfoveal choroidal thickness and mean thickness of Haller layer were significantly greater in CSC than in fellow eyes (P = 0.043 and P = 0.036, respectively) and in normal control eyes (P < 0.001 each), and those of fellow eyes in CSC patients were significantly thicker than those in normal control eyes (P = 0.018 and P = 0.017, respectively). The thickness of Sattler layer did not differ significantly among these groups (P = 0.519). CONCLUSION: Subfoveal choroidal thickness and the thickness of Haller layer were increased not only in affected but also in uninvolved fellow eyes of CSC patients. Nonvascular smooth muscle cells of the choroid may play a role in the pathophysiology of CSC, in response to increased sympathetic tone.

PROTECTIVE EFFECTS OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS ON PROGRESSION OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES.

PURPOSE: To investigate the effects of dipeptidyl peptidase-4 (DPP4) inhibitors on the progression of diabetic retinopathy (DR) in patients with Type 2 diabetes based on the DR severity scale. METHODS: The medical records of 82 patients with Type 2 diabetes enrolled from 2005 to 2015 were retrospectively reviewed. Fundus photographs were graded using Early Treatment Diabetic Retinopathy Study methods. The associations between baseline risk factors and progression of DR were investigated. RESULTS: Seven of 28 patients treated with DPP4 inhibitors and 26 of 54 treated with other hypoglycemic agents showed progression of retinopathy, defined as one or more steps on the Early Treatment Diabetic Retinopathy Study scale (P = 0.043). Only treatment with DPP4 inhibitors significantly reduced the progression of DR in patients after propensity score matching (P = 0.009). Treatment with DPP4 inhibitors was associated with a lower risk of DR progression (P = 0.011). CONCLUSION: Treatment with DPP4 inhibitors was the independent protective factor against the progression of DR, aside from improving glycemic control. This is the first study to show the benefits of DPP4 inhibitors in reducing DR progression, and provides encouraging preliminary data for further evaluation of DPP4 inhibitors in the progression of DR in a randomized, double-blind, placebo-controlled trial.

Corrigendum to "Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice".

[This corrects the article DOI: 10.1155/2017/1763292.].

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.

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.

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.

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.