Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Predicting retinal sensitivity using optical coherence tomography parameters in central serous chorioretinopathy.

PURPOSE: To predict changes in retinal sensitivity using optical coherence tomography (OCT) in eyes with central serous chorioretinopathy (CSC). METHODS: Twenty-three eyes in 23 patients with CSC were enrolled. Retinal sensitivity was measured twice using microperimetry in all the examined eyes. Spectral domain OCT measurements were simultaneously conducted. The relationship between retinal sensitivity and the thicknesses of (i) the retinal nerve fiber layer plus the ganglion cell layer (RNFL + GCL), (ii) the inner nuclear layer (INL), (iii) the outer nuclear layer (ONL), and (iv) the serous retinal detachment height (SRDH) were investigated in a point-wise manner. The associations between the change in retinal sensitivity and the OCT parameters at baseline were also investigated. RESULTS: The mean age of the participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p < 0.001), and the mean retinal sensitivity (p < 0.001) was significantly higher at the second examination, compared with the first; however, the logMAR visual acuity (VA) did not differ significantly between the two examinations (p = 0.063). The logMAR VA was associated with retinal sensitivity at both the first and second examinations (p < 0.001). The retinal sensitivity at the second examination was significantly correlated with the retinal sensitivity, RNFL + GCL, INL, ONL, and SRDH at the first examination and with the improvement in SRDH. CONCLUSIONS: Retinal sensitivity was associated with the retinal structure in eyes with CSC; these parameters could be useful for predicting the change in visual function prior to treatment.

LOCATIONAL AGREEMENT OF NEAR-INFRARED AUTOFLUORESCENCE WITH CHOROIDAL VASCULAR HYPERPERMEABILITY IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH. METHODS: Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated. RESULTS: This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]). CONCLUSION: Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.

The usefulness of the retinal sensitivity measurement with a microperimetry for predicting the visual prognosis of branch retinal vein occlusion with macular edema.

PURPOSE: To evaluate the usefulness of the retinal sensitivity in branch retinal vein occlusion (BVO) with macular edema (ME) following the anti-vascular endothelial growth factor (anti-VEGF) treatment. METHODS: Best-corrected visual acuity (BCVA), microperimetry, and optical coherence tomography (OCT) measurements were carried out in 20 patients with BVO with ME, at baseline and 1 month after the anti-VEGF treatment. The relationships among BCVA, mean retinal sensitivity (MS), macular volume (MV), central retinal thickness (CRT), integrity of ellipsoid zone (EZ), mean retinal sensitivity in the most affected quadrant (qMS), and macular volume in the most affected quadrant (qMV) were investigated. In addition, the relationships among the change in BCVA at 1 month (ΔBCVA1m), mean sensitivity in the most affected quadrant at 1 month (ΔqMS1m), MV in the most affected quadrant at 1 month (ΔqMV1m), and CRT at 1 month (ΔCRT1m) were analyzed. The optimal model for BCVA at 3 months after the treatment (BCVA3m) was identified. RESULTS: There was not a significant difference in BCVA (paired Wilcoxon test, p = 0.058) between at baseline and after the treatment, but there were significant differences in MS, MV, CRT, qMS, and qMV (p < 0.05). There was a significant relationship between ΔqMS1m and ΔMV1m, ΔCRT1m, and ΔqMV1m, respectively. ΔMS1m or ΔqMS1m and BCVA at baseline and ΔBCVA1m were selected as explanatory variables in the optimal model for BCVA3m. CONCLUSION: Retinal sensitivity was related to retinal structure, whereas this was not the case with BCVA. In addition, retinal sensitivity was useful to predict BCVA after anti-VEGF therapy.

Retinal sensitivity and fundus autofluorescence in adult-onset foveomacular vitelliform dystrophy.

The present study aimed to compare retinal sensitivity (RS) at each stage and to evaluate the relationship between RS and fundus autofluorescence (FAF) pattern in adult-onset foveomacular vitelliform dystrophy (AOFVD). We retrospectively reviewed 17 eyes of 13 patients with AOFVD. In addition to best-corrected visual acuity (VA), RS within the affected lesion and optical coherence tomography (OCT) measurements were carried out in each participant. All the examined eyes were classified into 4 stages and 3 FAF patterns. RS was superimposed on OCT fundus image and RS within the affected lesion was calculated in each eye. The relationships between visual functions (VA and RS within the affected lesion) and stages and also FAF patterns were analyzed using the linear mixed model. As a result, RS within the affected lesion was significantly associated with FAF pattern, but not with stage. In contrast, VA was correlated with neither stages nor FAF patterns. Our current result suggested that RS within the affected lesion was related to FAF patterns but this was not the case with VA in eyes with AOFVD, demonstrating the usefulness of measuring RS, not only VA, to comprehend the disease status in AOFVD.

Longitudinal anatomical and visual outcome of macular telangiectasia type 2 in Asian patients.

Limited information regarding the anatomical and visual prognosis of macular telangiectasia (MacTel) type 2 in the Asian population is currently available. Herein, we conducted a retrospective longitudinal analysis of Japanese patients diagnosed with MacTel type 2. Disease progression was evaluated using the Simple MacTel Classification developed by Chew EY et al. in 2023, and its association with visual changes was analyzed. Sixteen eyes of eight Japanese patients were included in the study, with an average follow-up period of 8.2 ± 3.9 years (range, 2.2-14.0). At the initial visit, 7 (44%) and 5 (31%) eyes were classified as Grade 2 (central ellipsoid zone break) and Grade 3 (noncentral pigment), respectively. The proportion of eyes that progressed by 1 or 2-steps in grade after 1, 3, 5, 8, and 12 years was 0%, 14%, 43%, 70%, and 100%, or 0%, 7%, 7%, 30%, and 75%, respectively. The visual acuity significantly deteriorated during the follow-up period, particularly in the two eyes with full-thickness macular holes (FTMH). Three out of 7 patients exhibited low serum serine concentrations, although no apparent correlation with anatomical or visual outcomes was observed. Overall, this cohort demonstrated chronic disease progression, both anatomically and functionally, in eyes with MacTel type 2, with FTMH potentially associated with greater visual loss.

Roles of Sphingosine Kinase and Sphingosine-1-Phosphate Receptor 2 in Endotoxin-Induced Acute Retinal Inflammation.

PURPOSE: To investigate the roles of sphingosine kinases (SphKs) and sphingosine-1-phosphate receptors (S1PRs) in endotoxin-induced uveitis (EIU) mice. METHODS: EIU model was induced using an intraperitoneal injection of lipopolysaccharide (LPS). The expression of SphKs and S1PRs in the retina was assessed using quantitative polymerase chain reaction (qPCR) and immunofluorescence. The effects of S1PR antagonists on the expression of inflammatory cytokines in the retina were evaluated using qPCR and western blotting. Effects of leukocyte infiltration of the retinal vessels were evaluated to determine the effects of the S1PR2 antagonist and genetic deletion of S1PR2 on retinal inflammation. RESULTS: Retinal SphK1 expression was significantly upregulated in EIU. SphK1 was expressed in the GCL, IPL, and OPL and S1PR2 was expressed in the GCL, INL, and OPL. Positive cells in IPL and OPL of EIU retina were identified as endothelial cells. S1PR2 antagonist and genetic deletion of S1PR2 significantly suppressed the expression of IL-1α, IL-6, TNF-α, and ICAM-1, whereas S1PR1/3 antagonist did not. Use of S1PR2 antagonist and S1PR2 knockout in mice significantly ameliorated leukocyte adhesion induced by LPS. CONCLUSION: SphK1/S1P/S1PR2 signaling was upregulated in EIU and S1PR2 inhibition suppressed inflammatory response. Targeting this signaling pathway has potential for treating retinal inflammatory diseases.

Risk Factors and Treatment Strategy for Retinal Vascular Occlusive Diseases.

Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and neovascular glaucoma. Even though anti-vascular endothelial growth factor therapy is the current established first-line of treatment for retinal vein occlusion, several clinical studies have been performed to identify better treatment protocols and new therapeutic options. In this review, we summarize the current findings and advances in knowledge regarding retinal occlusive diseases, particularly focusing on recent studies, in order to provide an update for a better understanding of its pathogenesis.

The effects of antithrombotic therapy in ab interno trabeculotomy with a spatula-shaped microhook.

To evaluate the effects of the discontinuation of antithrombotic drugs on intraocular pressure (IOP) reduction and complications from ab interno trabeculotomy for patients with glaucoma. We performed a retrospective chart review on the data of patients treated with antithrombotic agents who have undergone ab interno trabeculotomy through Tanito microhook combined with cataract surgery at the Asahi General Hospital and the Tokyo University Hospital, with 6 months of follow-up. The patients were classified into two groups depending on whether they discontinued (AT-) or continued (AT+) antithrombotic therapy during the perioperative phase. The demographics, pre- and postoperative IOP, medication score, best-corrected visual acuity (BCVA), and postoperative complications were analyzed preoperatively and postoperatively at 1 week and 1-6 months. The series included 44 eyes from 44 Japanese patients. The AT- and AT+ groups included 21 eyes from 21 patients and 23 eyes from 23 patients, respectively. The decrease in IOP from the baseline at 1 week postoperative was significantly different between the two groups (p = 0.009), but there were no significant differences observed in the other visits. Hyphema and IOP spikes exceeding 30 mmHg occurred in 10% and 10% of AT- participants, and in 43% and 26% of AT+ participants, respectively. Hyphema and spikes with hyphema occurred more frequently in the AT+ than in the AT- group (p = 0.02 and p = 0.05). The number of patients who had spikes was not significantly different (p = 0.27). In trabeculotomy using the Tanito microhook®, discontinuing antithrombotic therapy had better IOP-lowering effects and less postoperative complications.

Comparison of effectiveness and complications in trabeculotomy with phacoemulsification between ab externo and ab interno using a spatula-shaped microhook.

To compare the short-term surgical effectiveness and safety profile of trabeculotomy ab externo and ab interno with microhook in terms of the recovery of visual acuity. A retrospective chart review was performed on patients who underwent trabeculotomy combined with phacoemulsification and lens implantation at Asahi General Hospital, with 6 months of follow-up. The patients treated by trabeculotomy were classified into two groups depending on the surgical procedures: ab interno with Tanito microhook (TMH) and ab externo with rigid probe trabeculotome (LOT). The demographics, preoperative and postoperative intraocular pressure (IOP), number of medications (Med), best-corrected visual acuity (BCVA), surgical-induced astigmatism (SIA), and postoperative complications were analyzed at pre-operation, and 1 week and 1-6 months post-operation. Fifty-two eyes of 38 Japanese patients underwent TMH and 42 eyes of 32 patients underwent LOT. The decreases in IOP and Med from the baseline were significant at all time points in both groups (p < 0.001), but there were no significant differences between the two groups. BCVA improved significantly in TMH and LOT after the operation (p < 0.001). BCVA and SIA significantly improved, mostly at 1 week in TMH, compared with LOT (p = 0.02 and 0.003). Hyphema and IOP spike exceeding 30 mmHg (spike) occurred in 11% and 6% of participants in TMH, and 33% and 26% of participants in LOT, respectively. Hyphema and IOP spike occurred more frequently in the LOT than in the TMH group (p = 0.01 and 0.005). Ab interno trabeculotomy showed similar IOP-lowering effects as ab externo, but had less postoperative complications.

Correlation between fundus autofluorescence and visual function in patients with cone-rod dystrophy.

This study aimed to investigate the relationship between autofluorescence (AF) signal measured with ultra-wide field imaging and visual functions in patients with cone-rod dystrophy (CORD). A retrospective chart review was performed for CORD patients. We performed the visual field test and fundus autofluorescence (FAF) measurement and visualized retinal structures with optical coherence tomography (OCT) on the same day. Using binarised FAF images, we identified a low FAF area ratio (LFAR: low FAF/30°). Relationships between age and logMAR visual acuity (VA), central retinal thickness (CRT), central choroidal thickness (CCT), mean deviation (MD) value, and LFAR were investigated. Thirty-seven eyes of 21 CORD patients (8 men and 13 women) were enrolled. The mean patient age was 49.8 years. LogMAR VA and MD were 0.52 ± 0.47 and - 17.91 ± 10.59 dB, respectively. There was a significant relationship between logMAR VA and MD (p = 0.001). LogMAR VA significantly correlated with CRT (p = 0.006) but not with other parameters. Conversely, univariate analysis suggested a significant relationship between MD and LFAR (p = 0.001). In the multivariate analysis, LFAR was significantly associated with MD (p = 0.002). In conclusion, it is useful to measure the low FAF area in patients with CORD. The AF measurement reflects the visual field deterioration but not VA in CORD.

Visual outcomes and prognostic factors of vitrectomy for lamellar macular holes and epiretinal membrane foveoschisis.

PURPOSE: To evaluate the visual outcomes of vitrectomy for lamellar macular hole (LMH) and epiretinal membrane (ERM) foveoschisis and to investigate the prognostic factor for postoperative visual acuity. METHODS: We retrospectively reviewed 15 LMH and 17 ERM foveoschisis eyes that had undergone a standard three-port pars plana vitrectomy with (12 eyes) or without (20 eyes) cataract surgery. Best-corrected visual acuity (BCVA) at postoperative three months and the final visit were compared to the preoperative measurements. We investigated the relationship between BCVA at the final visit and baseline parameters (age, preoperative BCVA, the presence of epiretinal proliferation [EP] and ellipsoid zone [EZ] disruption). The best explanatory variables for the final BCVA were investigated using the corrected Akaike information criterion (AICc) model selection. RESULTS: The mean age was 67.2 years. The mean follow-up duration was 30.7 months. Fifteen of 32 examined eyes were diagnosed as LMH and 17 eyes as ERM foveoschisis. Twelve eyes in LMH had EP and 13 eyes showed the disruption of EZ integrity. In total, BCVA significantly improved at 3 months postoperatively (p = 0.0013). A significant improvement was observed in ERM foveoschisis (p = 0.0085) but not in LMH group (p = 0.071). Comparing the BCVA between the baseline and the final visit, significant improvements were observed in total, ERM foveoschisis and LMH group (p<0.001, p<0.001 and p = 0.026, respectively). The optimal model for BCVA at the final visit included preoperative BCVA and the presence of EZ disruption (p<0.001 and p<0.001, respectively). CONCLUSION: Our results suggested that the final BCVA was dependent on preoperative BCVA and the presence of EZ disruption. Surgical indications might be warranted for LMHs with EZ disruption.

Assessment of the choroidal structure in pregnant women in the first trimester.

We investigated the anatomical differences in the choroidal structure between pregnant women in the first trimester of pregnancy and age-matched healthy nonpregnant women using enhanced depth imaging optical coherence tomography (EDI-OCT) and choroidal binarization analysis. The main parameters measured in the two study groups, namely, pregnant women in the first trimester and healthy nonpregnant women, were choroidal thickness and the choroidal luminal area. Binarization of the EDI-OCT images from each patient was performed, and the choroidal vascularity index (CVI) was calculated. The correlations between the baseline characteristics of the subjects and the CVI were investigated using linear mixed model analysis. As a result, there was no statistically significant difference in the mean age, best-corrected visual acuity, axial length, central retinal thickness, subfoveal choroidal thickness, systolic blood pressure (BP), or diastolic BP between the two study groups. Conversely, a significant difference was observed in the CVI (P = 0.012) between the two groups. The multivariate analysis identified a significant correlation between the CVI and the systolic BP (P = 0.0044, linear mixed test). Taken together, a larger choroidal luminal area was associated with a higher systolic BP, especially in the first trimester of pregnancy. Our findings may provide further insight into the choroidal changes that occur during pregnancy.

Comparison between blue-on-yellow and white-on-white perimetry in patients with branch retinal vein occlusion.

This study aimed to compare blue-on-yellow (B/Y) perimetry with white-on-white (W/W) perimetry in eyes with branch retinal vein occlusion (BRVO). The following measurements were performed in 29 eyes of 29 patients with resolved BRVO: W/W and B/Y perimetries using 10-2 test grid, retinal volume (RV) using optical coherence tomography (OCT), and vessel densities (VD) of the superficial capillary layer (VDs) and deep capillary layer (VDd) using OCT angiography (OCTA). First, the difference in the retinal sensitivity (RS) between BRVO-affected and unaffected areas was compared between RS_B/Y and RS_W/W in the parafoveal and extrafoveal areas. Moreover, the structure-function relationship between vessel density and RS was compared between B/Y and W/W perimetries (RS_B/Y and RS_W/W, respectively). The difference in RS between BRVO-affected and unaffected areas was significantly larger with RS_B/Y than with RS_W/W in both the parafoveal and extrafoveal areas. In the parafoveal area, VDs, VDd, and RV were significantly correlated with both RS_W/W and RS_B/Y. In contrast, in the extrafoveal area, only VDd was included in the optimal models. Our findings suggest that RS_B/Y more strongly reflects the anatomical structure and BRVO-affected area.

The association between visual function and retinal structure in chronic central serous chorioretinopathy.

The purpose of the current study was to investigate the association between visual function and retinal structure in central serous chorioretinopathy (CSC). In 22 eyes of 22 chronic CSC patients with serous retinal detachment at the macula, retinal sensitivity was measured using MP3 microperimetry (NIDEK, Japan) and mean sensitivity within two degrees (MS2), four degrees (MS4) and six degrees (MS6), as well as foveal sensitivity (MS0), were calculated. Retinal structure was measured using optical coherence tomography (OCT, Spectralis, Heidelberg). The relationship between visual function (LogMAR best-corrected visual acuity [LogMAR VA] and MS0, MS2, MS4, MS6) and serous retinal detachment height at the fovea (SRDH), central retinal thickness (CRT), macular volume (MV) and central choroidal thickness (CCT) was investigated. There were significant negative correlations between LogMAR VA and MS0 (p = 0.016), MS2 (p = 0.049). No significant relationship was observed between LogMAR VA and SRDH (p = 0.97) although there was a significant negative correlation between SRDH and MS2 (p = 0.028), MS4 (p = 0.049), MS6 (p = 0.023). In conclusion, in CSC, serous retinal detachment was significantly correlated with retinal sensitivity measured with MP3, but not with LogMAR VA.