Journal of Ocular Pharmacology and Therapeutics

SIGHT compared intravitreal aflibercept injections (IAI) with photodynamic therapy (PDT) in Chinese patients with predominantly classic choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD).

Patients were randomized 3:1 to IAI (2 mg every 8 weeks after 3 initial monthly injections)/sham PDT or active PDT/sham IAI (with switch to IAI at week 28). We report the primary outcome (mean change in best-corrected visual acuity [BCVA] at week 28) and final 52-week outcomes.

Patients were randomized to IAI (n = 228) or PDT (n = 76) (mean age: 65.1 years). Mean BCVA change was +14.0 (IAI) versus +3.9 letters (PDT→IAI) (week 28) and +15.2 versus +8.9 letters (between-group difference: 6.2 letters; P = 0.0009) (week 52); mean reduction in central retinal thickness was −189.6 versus −170.0 μm (week 52). The greatest improvements in BCVA with IAI were in youngest patients (<65 years), and in those with a smaller active component of the CNV lesion (<50% of lesion size). The most common ocular treatment-emergent adverse events (study eye; IAI vs. PDT→IAI) were macular fibrosis (11.8% vs. 6.6%) and visual acuity reduced (6.6% vs. 21.1%). Three treatment-emergent Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were observed but none was considered drug related.

IAI demonstrated superiority over PDT in Chinese nAMD patients. The benefits of IAI were maintained through week 52 in all patients, including subgroups, and in patients who switched from PDT to IAI. The incidence of adverse events was consistent with the known safety profile of IAI. Trial registration number NCT01482910.

To compare the incidence and timing of first recurrence between patients who were treated with ranibizumab and aflibercept in neovascular age-related macular degeneration (AMD).

This retrospective study included 120 patients who received the diagnosis of treatment-naive typical neovascular AMD or polypoidal choroidal vasculopathy (PCV) and were treated using either ranibizumab (n = 73) or aflibercept (n = 47). Recurrence within 10 months of the third injection was compared between the 2 treatment groups.

In all 120 patients, there was no difference in recurrence between the ranibizumab and the aflibecept groups (P = 0.846). One hundred five patients completed 12 months follow-up. In typical neovascular AMD, disease recurred in 69.6% (16/23) of patients in the ranibizumab group, with a mean period of 4.4 ± 1.8 months after the third injection. In the aflibercept group, the equivalent values were 68.8% (11/16) and 4.5 ± 1.4 months. In PCV, disease recurred in 72.5% (29/40) of patients in the ranibizumab group, with a mean period of 3.8 ± 1.7 months after the third injection. In the aflibercept group, the equivalent values were 69.2% (18/26) and 4.3 ± 2.0 months.

Although the incidence of recurrence was slightly higher and the duration between the third injection and the first recurrence was slightly shorter in patients treated using ranibizumab, the differences were not significant. Our results require confirmation in further studies.

To evaluate the effect of epiretinal membranes (ERMs), detected with spectral-domain optical coherence tomography (SD-OCT), on the outcome of antivascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD).

A total of 434 eyes with treatment-naive nAMD were retrospectively included and analyzed. All patients were administered an initial series of 3 monthly loading injections of ranibizumab or aflibercept, followed by further injections as required. The visual and anatomical outcomes were compared between the eyes with ERMs and those without. Features of ERMs at baseline assessed with SD-OCT were evaluated and correlated with visual outcomes.

Sixty-eight eyes (15.7%) with nAMD presented ERMs at baseline. The mean best-corrected visual acuity (BCVA) of these eyes, expressed as the logarithm of the minimum angle of resolution, improved from 0.75 ± 0.48 (Snellen equivalent: 20/112) to 0.59 ± 0.44 (20/77) after 12 months of treatment (P = 0.021). Central foveal thickness also decreased from 381 ± 191 μm to 294 ± 167 μm (P < 0.001). Compared to the eyes without ERMs (366 eyes), the eyes with ERMs had a significantly thicker central fovea after treatment (P = 0.020). However, the intergroup differences in BCVA improvement were not significant. No significant association was found between visual outcome after treatment and ERM features on OCT at baseline.

In eyes with nAMD, ERMs were infrequent. Central foveal thickness was significantly greater after anti-VEGF treatment in eyes with nAMD and ERMs. However, the presence of ERMs in eyes with nAMD did not affect visual outcome.

To explore the inhibitory effect of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) on retinal angiogenesis and its underlying molecular mechanisms in the mouse model of oxygen-induced retinopathy (OIR).

C57BL/6J mice were classified into three groups as control group, OIR nonintervention group, and OIR intervention group. Postnatal day 12 (P12) mice in OIR intervention group were received recombinant mouse IGFBP-rP1 (50, 100, and 200 ng/mL) intravitreal injection. Five days later, the proliferative neovascular responses were estimated by quantifying the new vessel areas in flattening retinal tissues stained by high molecular fluorescein isothiocyanate-dextran and counting the numbers of neovascular cell nuclei breaking through the internal limiting membrane in cross sections. Expressions of phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2), ERK1/2, and vascular endothelial growth factor (VEGF) proteins in retinal tissues were assessed by western blot analysis.

Irregular neovascularization, nonperfusion region, and fluorescence leakage were observed in OIR models. The expression of retinal p-ERK1/2 and VEGF proteins were significantly upregulated in OIR nonintervention group compared with control group. The area ratio of retinal new vessels and the number of neovascular cell nuclei in OIR intervention group both decreased significantly, following the downregulation of retinal p-ERK1/2 protein expression and VEGF protein expression in a dose-dependent manner. Moreover, there was no significant difference in retinal ERK1/2 protein expression.

IGFBP-rP1 inhibits retinal angiogenesis by blocking ERK signaling pathway and downregulating VEGF expression in the mouse model of OIR. It highlights the potential importance of IGFBP-rP1 serving as a target of gene therapy for retinal neovascularization in the future.

To evaluate the real-world experience with half-time photodynamic therapy (PDT) versus half-dose PDT for chronic central serous chorioretinopathy (CSC).

This multicenter retrospective study enrolled patients who received half-time PDT (with irradiation time shortened to 42 s) or half-dose PDT (with the dosage of verteporfin reduced to 3 mg/m²) for chronic CSC and who were followed up for ≧12 months. The success rate, central subfield retinal thickness (CST), and best-corrected visual acuity (BCVA) were documented in each group of patients.

A total of 53 eyes from 49 patients were enrolled in this study. Seventeen eyes (15 patients) received half-time PDT and 36 eyes (34 patients) received half-dose PDT. The success rates in both groups were similar at 12 months (94.1% vs. 94.4%; P = 0.543). The mean CST at 1, 6, 12 months decreased significantly when compared with the baseline in both groups (all P < 0.001). The BCVA significantly improved at 6 and 12 months in both groups (all P < 0.05). There were no significant differences in changes of BCVA and changes of CST between the 2 groups at any time point.

Half-time PDT is a feasible treatment for chronic CSC. It has success rates similar to half-dose PDT at 12 months. There were no significant differences in changes of BCVA and changes of CST between the 2 groups at 1, 6, and 12 months after treatment.

To evaluate the effect of intravitreal dexamethasone implant (Ozurdex) treatment on serous macular detachment (SMD) in patients with nonischemic central retinal vein occlusion (CRVO).

Retrospective, interventional, noncomparative case series was conducted. Twenty-four eyes of 24 patients with macular edema (ME) and SMD secondary to nonischemic CRVO made up the study population. Patients who had received intravitreal triamcinolone and/or antivascular endothelial growth factor treatment and/or had undergone retinal photocoagulation were excluded from the study. After Ozurdex injection, visual and anatomical responses were observed.

The mean follow-up time was 9.96 ± 2.44 months (minimum 7, maximum 14). After injection of Ozurdex, ME and SMD regressed except for 1 patient. Twenty cases showed relapse within a 5.45 ± 1.43 months mean time. Seventeen of them had SMD. Eight cases revealed a second relapse and 1 case revealed a third relapse after retreatments. The mean time for the second relapse was 5.50 ± 1.19 months. The height of SMD was found to be lower in all follow-up examinations—including relapses—than baseline measurements. The median SMD value decreased from 247.5 μm (minimum 80, maximum 745) at baseline to 0 μm (minimum 0, maximum 426) at the final examination (P < 0.001). No eyes lost vision at any control visit. The mean best corrected visual acuity increased from 0.89 ± 0.31 logMAR at baseline to 0.62 ± 0.31 logMAR at the final examination (P < 0.01). No local or systemic complication was observed.

In this case series, Ozurdex was found as a safe and effective treatment for SMD and ME associated with nonischemic CRVO.

To examine whether butyroyloxymethyl-diethyl phosphate (AN-7), a histone deacetylase inhibitor, inhibits chemically induced corneal neovascularization (NV) in mice.

Corneal NV was induced in the right eye of male C57BL mice by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center. Immediately thereafter, the mice were randomized into 2 groups, receiving an intraperitoneal injection of AN-7 or saline, which served as control. Corneal NV was evaluated at constant time intervals from the corneal injury by corneal photographs and the area of corneal NV was measured. Centricity and density of the corneal vascularization were graded. Corneal flat mounts blood vessels staining and histological studies were performed on day 10. Unpaired t-test was used for group comparisons.

The corneal neovascular area was statistically significantly reduced by AN-7 treatment on days 10 and 14 postinjury and compared with the untreated group. The centricity and density of the corneal NV between treated and untreated groups showed no significant difference at any time point.

Systemic treatment with AN-7 had a significant inhibitory effect on chemical burn-induced corneal NV in mice. These results suggest that AN-7 should be further evaluated for its therapeutic potential for the treatment of corneal NV.

To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients.

Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate.

After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO₂; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05).

Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.

To investigate the short-term effects of 2 new secretagogue eye drops for dry eye, 3% diquafosol tetrasodium ophthalmic solution (diquafosol) and 2% rebamipide ophthalmic suspension (rebamipide), on the concentration of mucin 5AC (MUC5AC) in rabbit tear fluid and conjunctival goblet cells.

One dose of artificial tears, diquafosol or rebamipide, was instilled into 8 eyes of Japanese white rabbits. MUC5AC concentration in the tear fluid was examined using the enzyme-linked immunosorbent assay 15 min after instillation and compared with 8 untreated controls. Impression cytology was performed to measure the number of periodic acid Schiff (PAS)-positive cells and the ratio of the PAS-positive area using image analysis software. Statistical comparison was performed using ANOVA with post hoc analysis with the Tukey's test.

After 15 min, only diquafosol significantly (P ≤ 0.01) increased the MUC5AC level in the tear fluid. Although no drug affected the number of PAS-positive cells, the ratio of the PAS-positive area decreased significantly (P ≤ 0.01) only in the diquafosol group.

These data indicated that more PAS-positive MUC5AC was released into the tear fluid from the goblet cells by diquafosol than by rebamipide. There is a difference in the induction pattern of MUC5AC into the tears from the goblet cells between these eye drops.