Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

PURPOSE: To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. RESULTS: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. CONCLUSION: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Changes in intraocular pressure following intravitreal dexamethasone implant in patients with history of glaucoma filtration surgery.

PURPOSE: This study aimed to evaluate changes in intraocular pressure following intravitreal dexamethasone implant injection, specifically in patients undergoing glaucoma filtration surgery. METHODS: The degree of increase in intraocular pressure was compared retrospectively among three groups. Group 1 comprised patients who underwent prior glaucoma filtration surgery (54 eyes). Group 2 included patients with or suspected glaucoma without such surgical history (20 eyes). Group 3 included patients without glaucoma (33 eyes). Pressure measurements were taken before the injection and at 1, 2, 3, and 6 months post-injection. A subgroup analysis was performed for pressure > 35 mmHg, > 30 mmHg, > 25 mmHg, and a difference > 10 mmHg between the peak and baseline pressure. RESULTS: Group 1 consistently displayed lower pressures compared with Group 2, with significant difference at both 1- and 6-month post-injections (15.09 mmHg vs. 18.10 mmHg, P = 0.042 and 13.91 mg vs. 17.25 mmHg, P = 0.040). The proportion of patients in Group 1 and Group 3 with pressures > 25 mmHg, > 30 mmHg, and a difference > 10 mmHg did not significantly differ (15.6% vs. 9.5%, P = 0.231; 3.1% vs. 2.3%, P = 0.867; and 17.1% vs. 7.1%, P = 0.231). Notably, Group 2 exhibited a significantly higher proportion within each category (> 25 mmHg, 24.0%; > 30 mmHg, 20.0%; > 10 mmHg difference, 28.0%). CONCLUSION: Intravitreal dexamethasone implant did not increase the risk of elevated intraocular pressure in patients with a history of glaucoma filtration surgery compared with patients with suspected glaucoma; the risk was similar to those without glaucoma.

Spontaneous resolution of long-standing choroidal effusion after glaucoma drainage implant surgery without significant visual deterioration : a case report.

BACKGROUND: Choroidal effusion is a common complication of glaucoma surgery. Although most cases of choroidal effusions resolve spontaneously with observation or medical management alone as intraocular pressure normalizes, surgical drainage might be needed in severe or persistent cases. Herein, we report a case of spontaneous resolution of long-standing severe choroidal effusion after Ahmed glaucoma valve implantation. CASE PRESENTATION: An 85-year-old man with uncontrolled primary open-angle glaucoma and medical history of chronic kidney disease underwent uneventful Ahmed glaucoma valve implantation. On postoperative day 8, transient hypotony occurred, and large 360° peripheral choroidal detachments developed. Although the intraocular pressure increased to normal levels on postoperative day 15, choroidal effusion did not resolve. Fundus examination over 8 months showed that the large choroidal effusion persisted despite a well-controlled intraocular pressure. Laboratory test performed at preoperatively and follow-up period revealed persistently elevated potassium and creatinine levels. On postoperative 9 months, the lesion resolved spontaneously without any surgical intervention. We found that the patient's creatinine level was normalized, pre-existing hyperkalemia was corrected, and accordingly his general condition was improved. CONCLUSIONS: Considering the underlying medical condition may be helpful in patients with persistent choroidal effusion of an unclear etiology following glaucoma filtering surgery.

Predictors of treatment outcomes following treat-and-extend regimen with aflibercept for branch retinal vein occlusion: post-hoc analysis of the PLATON trial.

We investigated predictors of visual outcomes and injection interval in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) treated with a treat-and-extend (TAE) regimen. All 48 patients in a multicenter study were followed for 52 weeks and received three monthly intravitreal aflibercept injections before the TAE regimen, with treatment intervals adjusted by 4 weeks, up to a maximum of 16 weeks. Various laboratory biomarkers and optical coherence tomography parameters were evaluated. Patients were classified into the extension failure group if they had ≥ 1 treatment interval decreased due to an increase in the central macular thickness compared to the previous visit and 18 patients were assigned to this group. In multivariate logistic analyses, presence of microaneurysms and prominent middle limiting membrane (p-MLM) sign, increased initial external limiting membrane (ELM) disruption, and higher total cholesterol were correlated with inhibiting a sustained extension in the injection interval (P = 0.015, P = 0.032, P = 0.037, P = 0.009, respectively). Therefore, in the patients with ME secondary to BRVO with these risk factors, early consideration of frequent injection may improve treatment outcome.

Case Report: A case of ultra-late recurrence of KIF13A-RET fusion non-small cell lung cancer response to selpercatinib.

Background: Cancer recurrence remains a significant problem, and most postoperative recurrences of non-small cell lung cancer (NSCLC) develop within 5 years after resection. We present a rare case of ultra-late recurrence of NSCLC accompanying choroidal metastasis with KIF13A-RET fusion 14 years after the definitive surgery. Case description: A 48-year-old female patient who had never-smoked presented with decreased visual acuity. She had been treated with right upper lobe lobectomy followed by adjuvant chemotherapy 14 years prior. Fundus photographs revealed bilateral choroidal metastatic lesions. Positron emission tomography-computed tomography (PET-CT) scans showed extensive bone metastases and focal hypermetabolism in the left uterine cervix. An excision biopsy of the uterus showed primary lung adenocarcinoma with immunohistochemistry of TTF-1+. Plasma next-generation sequencing (NGS) identified the presence of KIF13A-RET fusion. After 6 months of selpercatinib therapy, PET-CT revealed a partial response for bone and uterine metastasis and stable disease for choroidal lesions. Conclusion: In this case report, we are reporting a rare case of ultra-late recurrence of NSCLC in a patient with choroidal metastasis. Furthermore, the diagnosis of NSCLC with RET fusion was based on liquid-based NGS rather than tissue-based biopsy. The patient showed a good response to selpercatinib, which supports the efficacy of selpercatinib as a treatment for RET-fusion-positive NSCLC with choroidal metastasis.

Short-Term Safety and Efficacy of Intravitreal Brolucizumab Injections for Neovascular Age-Related Macular Degeneration: A Multicenter Retrospective Real-World Study.

INTRODUCTION: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). METHODS: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. RESULTS: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. CONCLUSION: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months.

Influence of scan direction on subfoveal choroidal vascularity index using optical coherence tomography.

We investigated the influence of scan direction on subfoveal choroidal vascularity index (CVI) measurements using spectral-domain optical coherence tomography (SD-OCT) in young healthy subjects. Seventy-eight eyes of 41 healthy volunteers were included. Choroidal structures were obtained using SD-OCT with enhanced depth imaging (EDI) through radial scans at the center of the macula. The subfoveal choroidal images in the horizontal (0°), 45°, vertical (90°) and - 45° directions were recorded and CVIs were analyzed according to their respective directions using image binarization. Additionally, subfoveal choroidal thickness (SFCT), and axial eye length were measured. The SFCT and subfoveal CVI showed a negative correlation but were only significant for the 45° scan (Pearson's r = - 0.262, P = 0.021). The axial eye length and subfoveal CVI had no significant correlation in any direction (all P > 0.05). In the Bland-Altman plot, the subfoveal CVI measurement showed high agreement among the four scan directions. When the SFCT was ≥ 300 µm, there was no difference in the measured values of the subfoveal CVI among the four scan directions; however, when the SFCT was < 300 µm, there was a significant difference in subfoveal CVI among the scan directions (one-way analysis of variance, F = 4.685, P = 0.004). In subfoveal CVI measurement, it is considered that the horizontal (0°) scan can represent the vertical (90°) or oblique (45°, - 45°) scans. However, when the SFCT is thinner, the subfoveal CVI in each direction of radial scan may vary significantly. Hence, caution is required in the interpretation.

Comparison of the Structure-Function Relationship Between Advanced Primary Open Angle Glaucoma and Normal Tension Glaucoma.

PURPOSE: The aim was to investigate and compare the characteristics of visual field (VF) defects in primary open angle glaucoma (POAG) and normal-tension glaucoma (NTG) with advanced glaucomatous damage and to determine whether the structure-function relationships found in advanced glaucoma differ based on their glaucoma classification. PATIENTS AND METHODS: Ninety-seven eyes of 97 patients (59 eyes with POAG and 38 eyes with NTG) with advanced glaucoma were included in this cross-sectional study. Scores at each test point of the 30-2 VF total deviation map were recorded, and average values at each test point were point-wise compared between the groups. Peripapillary retinal nerve fiber layer (RNFL) and macular thickness (total, RNFL, ganglion cell layer, and inner plexiform layer thickness) were measured. The structure-function relationship based on the map of Garway-Heath was determined and compared between the 2 groups. RESULTS: At advanced stage of glaucoma, POAG eyes demonstrated more diffusely distributed VF defects, whereas NTG eyes had more severe VF defects at the superior nasal quadrant, showing increased asymmetry. Overall, peripapillary RNFL, macular ganglion cell layer, and macular inner plexiform layer thickness showed good relationships with 30-2 VF parameters in both groups. However, in total macula and macular RNFL thickness, the structure-function relationships tended to show different characteristics depending on the glaucoma classification; NTG eyes showed overall better relationships. CONCLUSIONS: In advanced glaucoma, differences in patterns of VF damage were found between POAG and NTG eyes. Conventional peripapillary RNFL and macular measurements showed generally good performance for estimating functional status, particularly in NTG eyes.

Tear Neuromediators in Subjects with and without Dry Eye According to Ocular Sensitivity.

To investigate differences of tear neuromediators between subjects with and without dry eye (DE) depending on the ocular sensitivity. Thirty-one subjects with DE and 29 subjects without DE were recruited in this study. The eyes were stimulated by exposure to an irritating product applied to the periocular region. Both DE and non-DE subjects were divided into the high sensitivity and low sensitivity groups based on the degree of ocular sensitivity to ocular irritation. Baseline tear film break-up time (TBUT) and corneal staining score were examined, and tear samples were collected. The concentrations of the tear neuromediators, including nerve growth factor (NGF), serotonin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide Y, and vasoactive intestinal peptide were measured using the enzyme-linked immune sorbent assay. The baseline neuromediator concentrations were compared between subjects with and without DE based on ocular sensitivity. In both DE and non-DE subjects, baseline TBUT was significantly lower in the high sensitivity group than in the low sensitivity group. In the high sensitivity group, baseline tear NGF levels were higher in subjects with DE than in those without DE. In the low sensitivity group, baseline levels of tear CGRP were lower in subjects with DE than in those without DE. Tear neuromediators associated with DE had differences in their concentrations depending on ocular sensitivity. In patients with DE, tear NGF levels increased with high ocular sensitivity to ocular irritation, whereas tear CGRP levels decreased with low ocular sensitivity.

Efficacy of Switching from Cyclosporine A 0.05% Anionic Emulsion to Cyclosporine A 0.1% Cationic Emulsion in Patients with Dry Eye Associated with Sjögren's Syndrome.

Purpose: To evaluate the clinical efficacy of switching from cyclosporine A (CsA) 0.05% anionic emulsion (CsA AE) to CsA 0.1% cationic emulsion (CsA CE) in patients with dry eye (DE) associated with Sjögren's syndrome (SS). Methods: Forty patients with SS-associated DE who were unresponsive to CsA AE for 6 months were enrolled. After baseline measurements, the CsA AE was switched to CsA CE. The ocular surface disease index (OSDI), Sjögren's International Collaborative Clinical Alliance (SICCA), and Schirmer's test scores and tear film breakup time (TBUT) were evaluated at baseline and 1 and 3 months after switching. Results: Two patients dropped out, and 38 were analyzed. OSDI and SICCA ocular staining scores were significantly reduced at 1 and 3 months after switching, compared with the baseline scores (all P < 0.01). Although no significant changes were noted in the corneal staining scores (CSSs), patients with higher baseline CSS (≥4) showed an improvement in the scores at 1 month (P = 0.03) and 3 months (P = 0.01) after switching. There were no significant changes in TBUT and Schirmer's test scores during the follow-up periods. Conclusions: In patients with SS-associated DE, switching from CsA AE to CsA CE was effective in improving ocular symptoms and conjunctival staining. In addition, corneal staining was decreased in patients with severe keratitis.

Prospective trial of treat-and-extend regimen with aflibercept for branch retinal vein occlusion: 1-year results of the PLATON trial.

PURPOSE: To evaluate the functional and anatomical outcomes of a treat-and-extend (TAE) regimen with aflibercept for treatment-naive macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: This was a prospective, multicenter, noncomparative, open-label clinical trial. Forty-eight eyes of 48 patients received three monthly intravitreal aflibercept injections prior to the TAE regimen. However, if the best-corrected visual acuity (BCVA) was ≥ 20/20 and the central macular thickness (CMT) was < 250 µm during the loading phase, the patient immediately proceeded to the TAE regimen. The treatment interval was adjusted by 4 weeks based on changes in CMT. The primary outcome was the mean change in BCVA from baseline to 52 weeks. RESULTS: The mean change in BCVA was 23.6 ± 14.2 letters. The proportion of patients with BCVA gain ≥ 15 letters was 77.1% at 24 weeks and 72.9% at 52 weeks. The mean reduction in CMT was 326.2 ± 235.6 µm at 24 weeks and 324.2 ± 238.0 µm at 52 weeks. The mean number of injections was 6.7 ± 1.2 (range: 6-11, all patients received three monthly intravitreal aflibercept injections) over 52 weeks, and 34 patients (70.8%) reached the maximal extension interval of 16 weeks at 52 weeks. CONCLUSIONS: The TAE regimen using aflibercept for ME secondary to BRVO, which has a treatment interval of up to 16 weeks, showed comparable efficacy to the fixed-dosing regimen along with reduced treatment burden.

Long-term outcomes of prediction error after combined phacoemulsification and trabeculectomy in glaucoma patients.

BACKGROUND: To investigate long-term outcomes of prediction error after phacotrabeculectomy and to determine risk factors that may cause unstable prediction error after phacotrabeculectomy in glaucoma patients. METHODS: A total 120 eyes of 120 patients who had underwent uncomplicated phacotrabeculectomy (combined group) or phacoemulsification (phaco-only group) were included. Best-corrected visual acuity (BCVA), intraocular pressure (IOP) were measured before and after surgery, and anterior segment parameters including anterior chamber depth (ACD), lens vault (LV), and anterior vault (AV) measured using anterior-segment optical coherence tomography were compared between the two groups. The mean absolute error (MAE) at 3, 6, 12, and 24 months postoperatively were compared. Risk factors associated with unstable prediction error (MAE ≥ 0.5) were investigated in the combined group. RESULTS: In both groups, BCVA was improved and IOP was decreased significantly. MAE at 3, 6, 12, 24 months postoperatively were not significantly different between two groups. The risk factors for unstable prediction error after 12 months of phacotrabeculectomy were old age and LV. Whereas, the only factor predicting unstable prediction error after 24 months of phacotrabeculectomy was LV. The cut-off value of LV for predicting unstable refractive error analyzed by the ROC curve was 0.855 mm. CONCLUSIONS: Phacotrabeculectomy may be an effective treatment with stable long-term outcomes of prediction error similar to phacoemulsification in patients with glaucoma. However, elderly patients or patients with large LV may be predisposed to unstable prediction error after phacotrabeculectomy.

Anterior Scleral Thickness in Myopic Eyes and Its Association with Ocular Parameters.

PURPOSE: This study was designed to determine whether the anterior scleral thickness is affected by axial elongation and to investigate the association between anterior scleral thickness and various ocular parameters in myopic eyes. METHODS: This cross-sectional study included 79 healthy myopic participants. Anterior scleral thickness was measured in 8 meridians (superior-nasal, superior, superior-temporal, temporal [T], inferior-temporal, inferior [I], inferior-nasal, and nasal [N]) using anterior segment optical coherence tomography. Bruch's membrane opening (BMO) area, width of ß-parapapillary atrophy with and without Bruch's membrane (PPA+BM and PPA-BM), and the global peripapillary and subfoveal choroidal thickness were additionally measured. Age- and sex-adjusted partial correlation analysis and linear regression analysis were performed to examine the effects of axial length and various ocular parameters on anterior scleral thickness in myopic eyes. RESULTS: The mean age of the included participants was 27.03 ± 2.70 years. Overall, the anterior scleral thickness varied topographically according to the meridians and distance from the scleral spur. In the partial correlation analysis controlled for the effect of age and sex, increasing axial length was related to anterior scleral thinning at several measurement points along the T, I, and N meridians. Among the several ocular parameters, multivariate linear regression analysis with age, sex, and axial length as covariates revealed that central corneal thickness, intraocular pressure, and BMO area were significantly associated with anterior scleral thickness. CONCLUSION: In conclusion, there was a close relationship between the anterior scleral thickness and several ocular parameters in myopic eyes. These features should be taken into consideration when managing myopia, and our results might have important implications for understanding the pathogenesis of scleral changes during axial elongation.

Effects of Eurya japonica extracts on human corneal epithelial cells and experimental dry eye.

Eurya japonica (EJ) leaves have been indicated to exert anti-oxidative and anti-inflammatory effects. Dry eye disease (DED) is a chronic inflammatory disease and oxidative stress is closely associated with DED. The aim of the present study was to analyze the therapeutic efficacy of EJ in DED using human corneal epithelial (HCE) cells and a mouse model of experimental dry eye (EDE). EJ extracts (0.001, 0.01 and 0.1%) were used to treat HCE cells. Cell viability and mitochondrial function were detected using a EZ-Cytox cell viability assay kit and mitochondrial membrane potential assays. Dichlorofluorescein diacetate (DCF-DA) assay was used to measure cellular reactive oxygen species (ROS) levels. Subsequently, eye drops consisting of BSS or 0.001%, 0.01 and 0.1% EJ extracts were applied for treatment of EDE. At 7 days, conjunctival ROS production was measured using a DCF-DA assay. Tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, 10 kDa interferon gamma-induced protein 10 (IP-10) and monokine induced by interferon-γ (MIG) levels in the conjunctiva were analyzed using a multiplex immunobead assay. Tear film and ocular surface parameters were measured. Treatment with EJ extracts in HCE cells effectively improved cell viability, ROS levels and mitochondrial function. Mice treated with 0.01 and 0.1% EJ extracts indicated a significant decrease in ROS, TNF-α, IL-1ß, IP-10 and MIG levels compared with the EDE or BSS groups. Furthermore, a significant improvement in all clinical parameters was observed in the 0.01 and 0.1% EJ extract groups. EJ extracts could decrease cytotoxicity and ROS production in HCE cells. Additionally, topical EJ extracts reduced oxidative damage and inflammation and improved clinical signs of EDE, suggesting that EJ extracts may be used as an adjunctive therapy for DED.

Impact of Scan Tilt on Quantitative Assessments Using Optical Coherence Tomography Angiography.

Purpose: To investigate the impact of scan tilt on quantitative assessments using swept-source optical coherence tomography angiography (SS-OCTA) in healthy participants. Methods: Healthy participants were imaged with a SS-OCTA system (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). After a standard scan was obtained, tilted scans were obtained by moving the optical coherence tomography beam entrance position horizontally. The tilting angle was measured from the B-scan image, and the flattest (horizontal) and the most tilted images were selected for comparative analysis. Foveal avascular zone (FAZ) area, vessel density (VD), and vessel length density (VLD) from the superficial and deep retinal capillary plexus (SCP, DCP), and choriocapillaris flow deficits (CC FDs) were computed and compared between horizontal and tilted images. Results: Thirteen eyes were excluded due to poor image quality or small angle difference (<8°) between the horizontal and tilted images. A final cohort of 27 normal eyes of 17 participants with a mean age of 39.3 ± 5.9 years was eligible for analysis. The FAZ area, VD, and VLD of both SCP and DCP were not significantly different between horizontal and tilted images. The CC FD, however, was significantly higher in horizontal images compared with tilted images (21.65% ± 2.41% vs. 21.06% ± 2.19%, P = 0.005). Conclusions: CC FD measurements may be significantly affected by the position of the scanning beam and resultant scan tilting. These findings highlight the importance of capturing on-axis (pupil-centered) scans for quantitative OCTA analyses. Translational Relevance: By assessing what impact a titled scan can have on OCTA measurements, this study will aid clinicians in understanding how to interpret their results in this situation.

Simple transscleral fixation of IOL technique without tying up haptics.

AIM: To introduce a novel technique for transscleral fixation of the posterior chamber intraocular lens (PC-IOL) that requires no sutures on the IOL haptics. METHODS: Instead of suturing polypropylene onto the IOL haptics, the method simply winds the thread on the haptics. Fifteen eyes of 15 patients underwent this technique and were followed up for more than 18mo. Surgical outcomes and post-operative complications were evaluated and compared with those of the conventional transscleral fixation method. RESULTS: Postoperative cylinder was significantly lower in the thread winding group than in the conventional transscleral fixation method group (-1.02±0.46 diopters vs -1.57±0.77 diopters; P=0.01). Further, no postoperative complications, such as optic capture, IOL dislocation, and hyphema, were detected in the thread winding group. CONCLUSION: We believe that our thread winding technique is better than previously reported methods because it is simple, mechanically stable, and free from suture-related complications.

Choriocapillaris flow deficit associated with intraretinal hyperreflective foci in intermediate age-related macular degeneration.

PURPOSE: To evaluate the choriocapillaris (CC) flow deficit (FD) beneath drusen associated with overlying intraretinal hyperreflective foci (HRF). METHODS: Patients with intermediate age-related macular degeneration (AMD) who had structural spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA) using the Cirrus HD-OCT with AngioPlex software were retrospectively evaluated. A 6 × 6-mm-volume scan was used for the SD-OCT and OCTA. Post-imaging processing steps included generation of drusen map, identification of HRF, and generation of a signal-compensated CC slab prior to binarization and CC FD computation. The CC OCTA image was aligned with the drusen + HRF map to define regions of interest for CC FD measurement. The CC was quantified below drusen with and without overlying HRF and within a 150-µm-wide ring surrounding the drusen (unaffected by potential HRF-related shadowing), and across the entire 6 × 6 macular region. RESULTS: Fifty-three eyes with intermediate AMD were included, 25 eyes with HRF, and 28 eyes with no HRF. The mean ± SD FD% over the whole 6 × 6 macular region was 41.1 ± 3.4 in eyes with HRF compared with 39.5 ± 3.5 in eyes without HRF (p = 0.001). The mean ± SD CC FD% below drusen with HRF (54.4 ± 9.3) was significantly greater than below drusen without HRF (49.6 ± 9.5; p = 0.001). There was a strong positive correlation between the quantity of HRF and the extent of the CC FD (Pearson correlation = 0.81). CONCLUSION: Choriocapillaris flow deficits appear to be more severe in eyes with HRF and in particular directly below HRF. As HRF are thought to represent a higher risk or more advanced feature of intermediate AMD, these findings highlight the relationship between the severity of CC FD and overall severity of AMD.

Effect of epidermal growth factor ointment on persistent epithelial defects of the cornea.

BACKGROUND: Healthy corneal epithelium acts as a barrier against damage to the deeper structures in the eye. Failure in the mechanisms of corneal epithelization can lead to persistent epithelial defects of the cornea (PEDs) and can compromise its function. Epidermal growth factor (EGF) promotes the proliferation, migration, and differentiation of epithelial cells, endothelial cells, and fibroblasts during wound healing and may be beneficial in treating patients with PEDs. We, therefore, investigated the effect of EGF ointment on patients with PEDs. METHODS: Fifteen patients with PEDs refractory to conventional treatment were treated twice a day with EGF ointment. Patient demographics and comorbidities were noted. The epithelial healing time was determined along with the primary outcome measures in the areas of the epithelial defects, visual acuity, visual analog scale (VAS) scores, and esthesiometer scores 1 month and 2 months after treatment. RESULTS: Five eyes of herpetic keratitis (33.3%), 3 eyes of dry eye disease (20.0%), 3 eyes of bacterial keratitis (20.0%), 2 eyes of limbal stem cell deficiency (13.3%), 1 eye of diabetic neurotrophic keratitis (6.7%), and 1 eye of filamentary keratitis (6.7%) were associated with PEDs, respectively. Two months following treatment with EGF ointment, there was a reduction in the area of the epithelial defects (5.7 ± 3.9 to 0.1 ± 0.3 mm2) as well as a significant improvement in best-corrected visual acuity (0.9 ± 0.8 to 0.6 ± 0.5 LogMAR) and VAS scores (4.5 ± 1.2 to 2.5 ± 0.7) in 12 eyes (80%). Among these cases, the mean epithelial healing time was 5.5 ± 1.8 weeks. Amniotic membrane transplantation was performed on the remaining 3 (20.0%) patients that did not respond to EGF treatment. CONCLUSIONS: EGF ointment could reduce symptoms and promotes corneal epithelialization of refractory PEDs. It may, therefore, be well-tolerated and a potentially beneficial addition in the management of refractory PEDs.

Quantitative assessment of the retinal microvasculature and choriocapillaris in myopic patients using swept-source optical coherence tomography angiography.

PURPOSE: To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Patients with high myopia (≥ - 6D; axial length ≥ 26.5 mm), moderate myopia (≥ - 3D, < - 6D), and age-matched healthy subjects presenting to the Shanghai General Hospital and Doheny-UCLA Eye Centers were enrolled in this prospective, multicenter study. Any subjects with evidence of macular abnormalities suggestive of pathologic myopia were excluded. SS-OCTA at both sites was performed using a Zeiss PLEX Elite instrument with a 6 × 6 mm scan pattern centered on the fovea. Two repeated volume scans were acquired for image averaging. The instrument pre-defined en face slab of the superficial and deep retinal capillary microvasculature was used to isolate and display the superficial and deep retinal capillaries. A slab spanning from 21 to 31 µm deep to the RPE fit line was used to isolate and display the CC. The OCTA images were exported for averaging using Image J. Littmann's method and the Bennett formula were applied to adjust for the impact of magnification in the high and moderate myopia groups. The resultant images were then binarized. Though projection artifact removal software was used, regions below the large superficial retinal vessels were excluded for quantitative analyses of the deep retinal capillary plexus and the CC. Vessel density (VD) and vessel length density (VLD) of the superficial and deep retinal capillary plexus (SCP, DCP) and CC flow deficit (FD) were analyzed, quantified, and compared between different groups. RESULTS: Twenty-five eyes of 25 patients with high myopia, 25 eyes of 25 patients with moderate myopia, and 25 eyes of 25 normal age-matched controls were included in this study. The VD of the SCP was lower in the high myopia group compared with the emmetropic control groups (p < 0.05), but the VD of the DCP demonstrated no significant difference among the three groups (p > 0.05). The VLDs of the SCP were lower in the high and moderate myopia groups compared with the control group (p < 0.05), while the VLD of the DCP was lower in the high myopia group compared with the moderate myopia and emmetropic control group (p < 0.05). The CC FD% in the high myopia group was significantly greater than both the control and moderate myopia subjects (p < 0.05). Of note, the severity of the CC flow deficit was not correlated with choroidal thickness (p > 0.05). CONCLUSION: The retinal microvasculature may demonstrate alterations in highly myopia eyes. The CC in macular regions shows greater impairment in eyes with high myopia compared with eyes with lesser degrees of myopia, and these deficits are already present in the absence of features of pathologic or degenerative myopia. The threshold of CC FD leading to myopic maculopathy remains to be defined.

Dll4 Suppresses Transcytosis for Arterial Blood-Retinal Barrier Homeostasis.

RATIONALE: Central nervous system has low vascular permeability by organizing tight junction (TJ) and limiting endothelial transcytosis. While TJ has long been considered to be responsible for vascular barrier in central nervous system, suppressed transcytosis in endothelial cells is now emerging as a complementary mechanism. Whether transcytosis regulation is independent of TJ and its dysregulation dominantly causes diseases associated with edema remain elusive. Dll4 signaling is important for various vascular contexts, but its role in the maintenance of vascular barrier in central nervous system remains unknown. OBJECTIVE: To find a TJ-independent regulatory mechanism selective for transcytosis and identify its dysregulation as a cause of pathological leakage. METHODS AND RESULTS: We studied transcytosis in the adult mouse retina with low vascular permeability and employed a hypertension-induced retinal edema model for its pathological implication. Both antibody-based and genetic inactivation of Dll4 or Notch1 induce hyperpermeability by increasing transcytosis without junctional destabilization in arterial endothelial cells, leading to nonhemorrhagic leakage predominantly in the superficial retinal layer. Endothelial Sox17 deletion represses Dll4 in retinal arteries, phenocopying Dll4 blocking-driven vascular leakage. Ang II (angiotensin II)-induced hypertension represses arterial Sox17 and Dll4, followed by transcytosis-driven retinal edema, which is rescued by a gain of Notch activity. Transcriptomic profiling of retinal endothelial cells suggests that Dll4 blocking activates SREBP1 (sterol regulatory element-binding protein 1)-mediated lipogenic transcription and enriches gene sets favorable for caveolae formation. Profiling also predicts the activation of VEGF (vascular endothelial growth factor) signaling by Dll4 blockade. Inhibition of SREBP1 or VEGF-VEGFR2 (VEGF receptor 2) signaling attenuates both Dll4 blockade-driven and hypertension-induced retinal leakage. CONCLUSIONS: In the retina, Sox17-Dll4-SREBP1 signaling axis controls transcytosis independently of TJ in superficial arteries among heterogeneous regulations for the whole vessels. Uncontrolled transcytosis via dysregulated Dll4 underlies pathological leakage in hypertensive retina and could be a therapeutic target for treating hypertension-associated retinal edema.