Pharmacotherapy for Macular Diseases

The aim of this study was to evaluate the efficacy of a treat-and-extend (T&E) regimen of ranibizumab as the first-choice treatment in macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). We conducted a retrospective study of 20 patients who developed MO due to BRVO treated with intravitreal ranibizumab in a T&E regimen between 2016 and 2017 with a minimum follow-up of two years. Patients were classified as complete responders if treated with ranibizumab alone or incomplete responders if salvage treatment with other medications or laser was needed. Data on best corrected visual acuity (BCVA) and central macular thickness (CMT) every 6 months were recorded. The mean BCVA (logMAR) improved from 0.60 ± 0.36 to 0.29 ± 0.44 and the CMT decreased from 559.85 ± 198.61 to 305.85 ± 11.78 μm. We found statistically significant differences between complete and incomplete responders on the average number of injections during the second year (2.46 ± 2.18 compared to 5.43 ± 1.27; p = 0.007) and change of the BCVA and CMT between both groups (p < 0.001) at 6, 12, 18 and 24 months. T&E seems to be effective in MO secondary to BRVO, improving visual function and decreasing CMT, with less need for injections. Full article

To evaluate choroidal volume and thickness changes after photodynamic therapy (PDT) for chronic central serous chorioretinopathy (CSC). Chronic CSC eyes with a history of PDT were selected. Average choroidal volume, average choroidal thickness, the maximum and minimum choroidal thickness of the macula irradiated area and peripheral non-irradiated areas before and after one and three months of treatment were examined. A total of 14 patients with chronic CSC and 9 controls without any eye pathology were enrolled. The mean choroidal volume in CSC before and, and after one and three months of treatment were 2.36 (standard deviation: 0.70), 1.90 (0.69), 1.86 (0.66) mm³ for the central area, 1.25 (0.38), 1.14 (0.35), 1.13 (0.34) mm³ for superior nasal area, 1.47 (0.41), 1.28 (0.43), 1.26 (0.43) mm³ for superior temporal area, 1.07 (0.49), 0.95 (0.38), 0.93 (0.35) mm³ for inferior nasal area, 1.17 (0.38), 1.04 (0.32), 1.03 (0.33) mm³ for inferior temporal area. This study revealed the choroidal volume changes in a short period after PDT and a decrease in unirradiated choroidal volume was also shown after the treatment. The algorithm provided on the ARI Network enables to evaluate the choroidal changes quantitatively and qualitatively. Full article

This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H₂O₂)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H₂O₂ induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H₂O₂ dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H₂O₂ elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H₂O₂-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H₂O₂-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease. Full article

This retrospective study was conducted to investigate the clinical factors associated with low-contrast visual acuity after reduced-fluence photodynamic therapy (RFPDT) in patients with resolved central serous chorioretinopathy (CSC) and good baseline visual acuity. A total of 45 eyes of 45 patients with resolved CSC at post-RFPDT and best-corrected visual acuity of >1.0 (logarithm of the minimal angle of resolution [logMAR], 0) at baseline were examined. Visual acuities of both eyes were measured at four contrast levels (100%, 25%, 12%, and 6%) at post-RFPDT. The low-contrast visual acuity (6%, 12%, and 25%) was significantly lower than the 100% contrast visual acuity in the affected eyes. Visual acuities of affected eyes were significantly worse than those of fellow eyes at any contrast levels. The degree of changes in 6% and 100% contrast visual acuities was significantly greater in affected eyes than that in fellow eyes (p < 0.05). The 6% contrast visual acuities in affected eyes at post-RFPDT were significantly associated with the symptom duration (p < 0.05). Patients with a long duration of symptoms might have disturbed low-contrast visual acuities at post-RFPDT even if their baseline visual acuities were good. Full article

Central serous chorioretinopathy (CSC) is a disease of unknown etiology, but half-dose photodynamic therapy (hPDT) is well known to be effective for CSC. Infrared reflectance (IR) has been shown to be effective for detecting retinal pigmented epithelial and choroidal lesions, but no reports have focused on chorioretinal changes using IR images after as compared to before hPDT. This study aimed to clarify the features of IR images as well as retinal and choroidal morphological changes before and after treatment with verteporfin hPDT for CSC. We also examined prognostic factors associated with CSC treatment. This was a retrospective study that included 140 eyes of 140 patients (male/female ratio 122:18, mean age 53.4 ± 10.8 years) diagnosed with CSC who underwent hPDT in our hospital during the period from April 2015 to December 2018. We determined changes in visual acuity, therapeutic efficacy, central retinal thickness (CRT), central choroidal thickness (CCT), and IR images at one and three months after hPDT as compared to before treatment. Dry macula was defined as a complete resolution of serous retinal detachment after hPDT. History of smoking, disease duration, presence of drusen, presence of retinal pigment epithelium abnormalities, type of fluorescein angiographic leakage, and presence of choroidal vascular hyperpermeability were investigated as prognostic factors associated with treatment efficacy. CRT and CCT were measured using optical coherence tomography (Spectralis HRA-2; Heidelberg Engineering), and IR images after versus before treatment were compared using ImageJ software (version 1.52) to calculate the mean luminance for a 3 × 3 mm area in the macula. Compared with the values before treatment, CCT, CRT, and visual acuity showed significant improvements at one and three months after treatment, and the mean luminance of IR images was also significantly increased. Furthermore, the luminance on IR images tended to rise, though the values at one month and three months after treatment did not differ significantly. Disease duration was significantly associated with dry macula one month after treatment, and visual acuity and CRT before hPDT were both significantly related to dry macula three months after treatment. IR images tended to improve over time, from before treatment through one and three months after hPDT. Full article

We investigated whether polygenic risk score (PRS) was associated with one-year outcome of as-needed aflibercept therapy for exudative age-related macular degeneration (AMD), including AMD (n = 129) and polypoidal choroidal vasculopathy (n = 132). A total of 261 patients were treated with as-needed intravitreal aflibercept injection (IAI) after three monthly IAIs and the completion of a one-year follow-up. One hundred and seventy-two healthy volunteers served as controls. Genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), SKIV2L-C2-CFB (rs429608), C3 (rs2241394), ADAMTS-9 (rs6795735) and CETP (rs3764261) was performed for all participants. A total of 63 PRSs were quantified. There was a positive association between the PRS involving ARMS2, CFH, C3, and ADAMTS-9 and best-corrected visual acuity at twelve months (p = 0.046, multiple regression analysis). When comparing PRSs of patients requiring retreatment and of patients without retreatment, 35 PRSs were significantly greater in patients requiring retreatment than in patients without requiring retreatment, with the PRS involving ARMS2 and CFH being most significantly associated (p = 1.6 × 10⁻⁴). The number of additional injections was significantly associated with 40 PRSs and the PRS involving ARMS2 and CFH showed a most significant p-value (p = 2.42 × 10⁻⁶). Constructing a PRS using a combination with high-risk variants might be informative for predicting the response to IAI for exudative AMD. Full article