Subfoveal choroidal thickness as a potential predictor of treatment response after intravitreal ranibizumab injections for polypoidal choroidal vasculopathy.

OBJECTIVE: To evaluate the impact of subfoveal choroidal thickness (SFCT) and other clinical biomarkers in intravitreal anti-vascular endothelial growth factor response in treatment-naive Caucasian patients diagnosed with polypoidal choroidal vasculopathy (PCV/AT1). DESIGN: Cross-sectional study. PARTICIPANTS: Treatment-naive patients diagnosed with PCV/AT1 recruited in a single centre from January 2013 to December 2020. METHODS: Eligibility was determined in treatment-naive PCV patients who received a loading dose of 3 injections of 0.5 mg ranibizumab. A diagnosis of PCV/AT1 was made based on the diagnostic criteria in the efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with sumptomatic macular polypoidal choroidal vasculopathy study. Choroidal thickness was manually measured by enhanced depth imaging technology in Spectralis spectral domain optical coherence tomography. RESULTS: Eighty-three eyes of 83 patients were included in this study, 47 patients diagnosed with PCV/AT1 with a good response to 3 intravitreal injections of ranibizumab and 36 with a poor response. The receiver operating characteristic curve of treatment effect against the SFCT revealed that the area under the curve was 0.85 (range, 0.74-0.96). Based on the Youden index, the optimal SFCT cut-off point for predicting a poor response to anti-vascular endothelial growth factor is 257 µm. In the multivariate analysis, the SFCT remained statistically significant (odds ratio 1.02 [range, 1.01-1.04]; P = 0.008). The combined effect of treatment effect against clinical biomarkers produced an area under the curve of 0.90 (range, 0.82-0.98). CONCLUSION: SFCT is a risk factor for a poor response to the 3 loading injections of ranibizumab in treatment-naive PCV/AT1 Caucasian patients. A cut-off point of 257 µm could be a valuable parameter for defining the population at risk for an inadequate response to ranibizumab.

Indocyanine green angiography findings in patients with neovascular age-related macular degeneration refractory to ranibizumab switched to aflibercept.

PURPOSE: To describe indocyanine green angiography (ICGA) and visual acuity (VA) results in patients with neovascular age-related macular degeneration (nAMD) refractory to ranibizumab switched to aflibercept. METHODS: This study is a prospective interventional case series. Thirty-two eyes of 32 patients with nAMD showing a poor response after at least 24 months of ranibizumab were switched to aflibercept. Twenty eyes had type I choroidal neovascularization (CNV group), and 12 eyes had polypoidal choroidal vasculopathy (PCV group). After an initial loading dose of three monthly aflibercept injections, treatment was continued on a treat-and-extend basis. ICGA was performed just before the first aflibercept injection (baseline) and 12 and 24 months later. The variables recorded were: closure of polyps and lesion area, VA, number of aflibercept injections, dry macula, and pigment epithelium detachment. RESULTS: The following means were recorded in the CNV and PCV groups, respectively: number of ranibizumab injections 20.4 ± 11.2 and 22.4 ± 12.9 (p = 0.740); baseline VA (before aflibercept) 73.2 ± 9.1 and 70.3 ± 13.7 letters (p = 0.654); and final VA 73.0 ± 7.6 and 69.3 ± 15.6 letters (p = 0.509). VA remained stable (p = 0.761 and 0.964) after 15.5 ± 3 and 15.1 ± 3.5 aflibercept injections (p = 0.244). At 24 months, dry macula was noted in 40 to 50% of the eyes (p = 0.620). Complete resolution of polyps was observed in 58% at 12 months and 92% at 24 months. CONCLUSIONS: In patients with nAMD refractory to ranibizumab, aflibercept was effective at maintaining VA and closing numerous polyps. In half of the patients, dry macula was observed at 24 months.

Long-Term Outcomes of Two Different Initial Dosing Regimens of Intravitreal Ranibizumab Used to Treat Myopic Choroidal Neovascularization.

PURPOSE: To compare two different initial dosing regimens of intravitreal ranibizumab used to treat myopic choroidal neovascularization. METHODS: A total of 61 eyes of 56 patients were treated: 26 eyes received a single injection followed by treatment pro re nata (1+ PRN), while 35 eyes first received 3 consecutive monthly injections (3+ PRN). RESULTS: The mean follow-up was 53 ± 16 months. The visual acuities were 51.9 ± 16.2 letters with 3+ PRN and 53 ± 22.4 letters with 1+ PRN at baseline (p = 0.824); 69.5 ± 12.3 and 69 ± 15.1 letters, respectively, at 12 months; and 67.1 ± 16.2 and 66.4 ± 19.7 letters, respectively, at the end of follow-up (p = 0.877). Mean survival until first retreatment after the loading dose was 36.9 ± 6.1 months with 3+ PRN and 19.2 ± 5.4 months with 1+ PRN (p < 0.001). CONCLUSIONS: Both dosing regimens led to similar visual outcomes. For eyes given a single injection in the first quarter, retreatment was needed appreciably earlier.

Retinal nerve fiber layer thickness changes in patients with age-related macular degeneration treated with intravitreal ranibizumab.

PURPOSE: To assess the effects of intravitreal ranibizumab therapy on intraocular pressure (IOP) and retinal nerve fiber (RNFL) thickness. METHODS: Forty-nine eyes of 49 patients with neovascular age-related macular degeneration (AMD) treated with intravitreal ranibizumab injections and 27 fellow eyes not requiring treatment were followed for 1 year. RNFL thickness, as measured by Fourier domain optical coherence tomography, and IOP were determined pre- and postinjection. RESULTS: After 12 months, the mean number of injections received was 4.8 ± 1.6. The incidence of IOP elevations (>5 mm Hg over baseline) observed at the time of injection was 0.4%. Baseline RNFL thickness was 105.7 ± 12.2 µm in the treatment group compared with 101.8 ± 11.6 µm in the control group (P = 0.176). At the end of follow-up, significant RNFL thinning was noted in the treatment group (100.2 ± 11.0 µm, P < 0.001), whereas no differences were found in the control group (100.5 ± 10.8 µm, P = 0.477). CONCLUSIONS: Intravitreal ranibizumab injections used to treat AMD caused a significant change in RNFL thickness after 12 months of follow-up.

Ranibizumab in retinal angiomatous proliferation (RAP): influence of RAP stage on visual outcome.

PURPOSE: To evaluate the influence of retinal angiomatous proliferation (RAP) stage on visual and anatomic outcome after ranibizumab (Lucentis®). METHODS: This was a prospective study on consecutively diagnosed RAP eyes at the Hospital Clínico San Carlos, Madrid. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) are performed monthly. Indocyanine green angiography (ICG) and fluorescein angiography (FA) are performed at baseline and every 3 months thereafter. A starting dose of a monthly ranibizumab injection in the first 3 months is followed by retreatment in case of intraretinal edema, subretinal fluid, or pigment epithelium detachment (PED) in OCT, increased leakage in FA, or a hot spot in ICG. RESULTS: A total of 53 eyes from 49 patients were included. The mean change in BCVA at 12 months was +7.3, +0.83, and -2.1 letters in stages IIA (21 cases), II B (18 cases), and III (14 cases), respectively. After adjusting the change in BCVA according to baseline BCVA, ß coefficient was -6.012 letters (p=0.025) in stage IIB and -9.762 letters (p=0.003) in stage III vs stage IIA. Four cases had a retinal pigment epithelium tear after injection of ranibizumab. CONCLUSIONS: Patients in stage II without PED have a better visual and anatomic evolution than patients in stage II with PED and stage III.

Intravitreal ranibizumab for myopic choroidal neovascularization: factors predictive of visual outcome and need for retreatment.

PURPOSE: To identify predictive factors for visual outcome and need for retreatment after treating myopic choroidal neovascularization (CNV) with ranibizumab. DESIGN: A prospective interventional case series. METHODS: Sixty-seven eyes of 67 patients with myopic CNV were treated with 3 intravitreal ranibizumab injections given monthly. Best-corrected visual acuity (BCVA) and optical coherence tomography-determined central macular thickness (CMT) were recorded monthly during follow-up. Fluorescein angiography changes and the number of injections needed were also assessed. RESULTS: Mean follow-up was 15.9 months. Mean BCVA improved by 7.8 letters after the first injection, 12.5 letters after 3 injections, and 12 letters by end follow-up. In 53 eyes (79.1%), BCVA improved; 40.3% gained more than 15 letters. No differences were detected in visual outcome between treatment-naïve and previously treated patients. Myopic CNV area and greatest linear dimension had diminished at the study end. The mean reduction in CMT was 93.6 µm. The mean number of injections given was 4.2. A total of 53.7% of eyes received only 3 injections. Through regression analysis, baseline BCVA (P = .006) and myopic CNV location (P = .026) were significantly correlated with BCVA at the end of follow-up. Myopic CNV location (P = .023) and prior treatment (P = .047) were significantly linked to the number of injections given. No major complications arose. CONCLUSION: An initial treatment regimen of 3 monthly ranibizumab injections seems effective and safe to treat myopic CNV. Baseline BCVA and myopic CNV location emerged as predictive factors for visual outcome. A need for retreatment was associated with myopic CNV location and prior treatment.

Comparison of ocular hypotensive actions of fixed combinations of brimonidine/timolol and dorzolamide/timolol.

OBJECTIVE: To compare brimonidine/timolol fixed combination (BrTFC; Combigan *) with dorzolamide/timolol fixed combination (DTFC; Cosopt dagger) in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG). METHODS: This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.5% twice daily, patients were randomized to BrTFC twice daily or DTFC twice daily for 6 weeks, before being crossed over to the other treatment arm for a further 6 weeks. At all follow-up visits, IOP was measured at 09.00 (pre-instillation) 12.00 and 16.00. The primary outcome measure was change in mean diurnal IOP from baseline at 6 weeks. The secondary outcome was percentage of patients with IOP <18 mmHg at 6 weeks. Data were analyzed from all patients who completed the study. RESULTS: Twenty-five patients were randomized and 20 completed the study. Mean diurnal IOP (mean +/- standard deviation [SD]) was 20.28 +/- 2.03 mmHg at timolol-treated baseline. After 6 weeks, mean diurnal IOP was 16.28 +/- 2.07 mmHg following BrTFC and 17.23 +/- 2.29 mmHg following DTFC (difference: 0.95 mmHg, 95% CI 0.10-1.80, p = 0.03). Mean IOP at 09.00 was 20.95 +/- 2.31 mmHg at baseline. This was reduced to 15.85 +/- 2.56 mmHg following BrTFC and 17.55 +/- 2.67 mmHg following DTFC (difference: 1.70, 95% CI 0.80-2.60, p = 0.001). For the 12.00 and 16.00 timepoints, the mean changes from baseline in the two arms were comparable. Percentages of patients achieving a target IOP of <18 mmHg were 85% following BrTFC and 60% following DTFC (p = NS [not significant]). No treatment-related adverse events were reported with either therapy. Key limitations include the small size of the study population and the 6-week duration of treatment periods, which prevents drawing conclusions regarding long-term therapy. CONCLUSION: Reductions from baseline in mean diurnal IOP and morning IOP were greater with BrTFC than with DTFC.

Early neovascular bridging of choroidal neovascularization after ranibizumab treatment.

BACKGROUND: To report three cases of early choroidal neovascularization (CNV) bridging after ranibizumab treatment. METHODS: Three patients with two separated foci of CNV secondary to age-related macular degeneration (ARMD), pathologic myopia and multifocal choroiditis were treated with monthly injections of ranibizumab por a period of 3 months. RESULTS: All three cases showed early coalescence across the fovea of the two neovascular foci, already 1 month after the first ranibizumab injection. Best-corrected visual acuity (BCVA) decreased in the three cases more than 20 letters due to early foveal involvement. CONCLUSIONS: Two different foci of CNV show a great tendency to decrease patients' vision because of neovascular bridging with foveal implication.