Patterns of anti-vascular endothelial growth factor discontinuation in neovascular age-related macular degeneration.

OBJECTIVE: To report on anti-vascular endothelial growth factor (anti-VEGF) discontinuation in neovascular age-related macular degeneration (nAMD). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive nAMD patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Demographics, treatment start and end dates, number of injections, treatment length, reason for discontinuation, and baseline and final data (i.e., age, best-corrected visual acuity, and central subfield thickness) were recorded. Statistical analyses using STATA 17.0 assessed differences between baseline and final values and between treatment-discontinuation subgroups. RESULTS: A total of 619 eyes of 502 treatment-naive patients (9015 injections) were included (age, 81.6 ± 8.4 years; 64.0% female). Discontinuation rate was 58.3% (361 of 619), with 310 patients discontinuing because of the lack of visual benefit (n = 152), severe comorbidity or death (n = 82), transferred (n = 33), stable off active treatment (n = 19), lack of benefit plus stable off treatment (n = 14), patient decision (n = 6), and ocular comorbidity (n = 4). Among the 309 remaining patients, 51 (16.5%) were lost to follow-up. Discontinuation occurred within the first year in 49.3% (n = 178). Visual acuity was at least maintained in all groups and improved in the following groups: severe comorbidity or death (p < 0.0001), lost to follow-up (p = 0.0003), transferred (p = 0.0004), and stable off treatment (p = 0.0053). The lack of visual benefit group had no improvement in vision regardless of treatment length. Compared with other subgroups, those stable off treatment group was younger (p = 0.0055), had better baseline vision (p = 0.0018), received more injections (p = 0.0437) over a longer time (p = 0.0034), and achieved better final vision (p < 0.0001). CONCLUSION: While there was a high discontinuation rate over 7.5 years, most were attributable to disease or treatment factors and nonmodifiable patient factors. Discontinuation frequently occurred within the first year.

Treatment discontinuation patterns of anti VEGF in retinal vein occlusion.

OBJECTIVE: The purpose of this research is to report on real-world anti-vascular endothelial growth factor (anti-VEGF) treatment patterns in retinal vein occlusions (RVO). DESIGN: Retrospective cohort study. PARTICIPANTS: Treatment-naive RVO patients initiating anti-VEGF injections between 2015 and 2021. METHODS: Medical records available until June 2022 were reviewed. Demographics, diagnosis, number of injections, treatment length, reason for discontinuation, and baseline and final data (e.g., date, age, best-corrected visual acuity [BCVA], and central subfield thickness) were recorded. Statistical analyses performed with STATA 17.0 assessed differences between baseline and final values, branch (BRVO) and central retinal vein occlusion (CRVO), and treatment-discontinuation subgroups. RESULTS: A total of 219 treatment-naive eyes were included (70.3 ± 13.2 years of age, 52.5% female), with 99 BRVOs and 120 CRVOs (2482 injections). The discontinuation rate was 76.7% (168 of 219), with 72.7% of patients (77 of 99) with BRVOs and 75.8% of patients (91 of 120) with CRVOs discontinuing injections. Reasons for discontinuation included stable off active therapy (98 eyes), severe comorbidity or death (17 eyes), switched to intraocular steroid (implant or injection) (12 eyes), lack of visual benefit (10 eyes), ocular comorbidity (5 eyes), patient decision (5 eyes), and patient transfer (5 eyes). Among the remaining 67 eyes, 16 (24%) were lost to follow-up. Reasons for discontinuation differed between BRVO and CRVO patients (p = 0.002). Eyes with CRVO presented with worse BCVA (p < 0.0001) and achieved worse final BCVA (p < 0.0001), but both groups experienced improvements (p < 0.0001). Younger age, better baseline BCVA, and a diagnosis of BRVO were independent predictors of better final visual acuity. CONCLUSION: Over 7.5 years, treatment was discontinued for three-quarters of RVOs. Stable disease was the most common reason for discontinuation, with nearly half (45%) of all RVOs in the cohort stable off active therapy. Better visual outcomes were achieved in BRVO than in CRVO, although both groups benefited from treatment.

The Canadian Ophthalmology Society's adaptation of the Medically Necessary Time-sensitive Surgical Procedures triage and prioritization tool.

At the start of the coronavirus disease 2019 (COVID-19) pandemic, hospitals and ambulatory surgical centres significantly decreased elective surgical procedures to facilitate capacity for in-hospital beds, preserve personal protective equipment (PPE), preserve anesthetic medications and limit spread of infection. Non-COVID-19­related ophthalmic disease continues to affect vision, and it is anticipated that the backlog of elective surgeries will require months to years to resolve. The delivery of ophthalmic surgical care in a prioritized, systematic and transparent way is vital to manage the surgical backlog while minimizing vision loss and consequent disability in the Canadian population. The Canadian Ophthalmology Society (COS) has modified the published Medically Necessary, Time Sensitive (MeNTS) Procedures scoring system to be applicable to all subspecialties within ophthalmology. This case prioritization process integrates medical necessity, consideration of resource preservation with risk of COVID-19 exposure, and factors unique to eye care. It provides guidance to Canadian ophthalmologists to facilitate decision making in triaging elective procedures.

The effectiveness of ocriplasmin versus surgery for the treatment of macular holes: A systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review looking at the effects of ocriplasmin compared to pars plana vitrectomy on macular holes to assess the effectiveness of the treatment options. METHODS: Literature was searched through MEDLINE, EMBASE, CINAHL, Clinical Trials.gov, and ProQuest Dissertations and Theses until June 12, 2018. Conferences held through Association for Research in Vision and Ophthalmology, Canadian Society of Ophthalmology, and American Academy of Ophthalmology were searched until June 18, 2018. A total of 208 records were screened leaving 26. One author independently reviewed them for quality and extracted data. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. The adverse events, MH closure rate, change in MH size, and the extent to which the patients' visual acuity is restored by each treatment option; ocriplasmin and vitrectomy. RESULTS: Twenty-six articles were included for qualitative and quantitative analysis. Meta-analysis results showed a 34% closure of macular holes after ocriplasmin treatment compared to 92% after vitrectomy. A significant improvement in visual acuity was seen after vitrectomy (SMD = -1.42; CI: [-1.98, -0.86]) as well as the ocriplasmin treatment (SMD = -0.73; CI: [-0.98, -0.48]). CONCLUSIONS: Results suggested 92% macular hole closure after vitrectomy compared to 34% after ocriplasmin. A significant improvement in visual acuity of patients was seen after both treatments. More good quality randomized controlled trials are required to make strong conclusions.

Two-year analysis of changes in the optic nerve and retina following anti-VEGF treatments in diabetic macular edema patients.

Purpose: To evaluate long-term structural and functional changes that happen to the optic nerve and retina following ranibizumab (Lucentis) injections in diabetic macular edema (DME) patients. Methods: Patients with clinically significant DME requiring anti-VEGF injections underwent pre-injection baseline, 6, 12, and 24 month follow-up tests. The tests performed were optical coherence tomography (OCT), best-corrected visual acuity (BCVA), and visual field (VF). Wide-field fluorescein angiogram (IVFA) was performed to monitor the progression of diabetic ischemia. Results: A total of 30 patients requiring anti-VEGF injections and 21 control patients not requiring anti-VEGF injections were enrolled in the study. From baseline, the average macular thickness significantly decreased (p<0.0002) over the 24-month time period. Mean perfused ratio significantly increased (p<0.0005) at 6, 12, and 24 months. Cup volume and vertical cup-to-disk ratio significantly increased (p<0.0014) over the study period. This was verified by masked independent grading of patient optic nerve stereo-photographs by glaucoma specialists. BCVA significantly (p<0.0006) improved over the study period. VFs showed a non-significant trend of deteriorating peripheral vision at 12 and 24 months. Conclusion: Clinically, anti-VEGF therapy appears to affect the optic nerve by increasing cup volume and increasing vertical cup/disk ratio over time. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Safety of anti-VEGF treatments in a diabetic rat model and retinal cell culture.

PURPOSE: To analyze the safety of different concentrations of anti-VEGF on retinal cells. METHODS: Non-diabetic and streptozotocin (STZ)-induced diabetic rats received intravitreal rat anti-VEGF injections that had final vitreous concentrations of 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL. Rats were also injected with the clinical dose of ranibizumab. TUNEL assay was performed on sectioned eyes to evaluate apoptotic cells. In vitro, rat retinal cell cultures were exposed to 0, 0.0625, 0.125 (clinical dose), and 0.25 mg/mL of ranibizumab for 48 and 72 hrs. Cellular metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, necrosis by lactate dehydrogenase (LDH), and apoptosis by cell death enzyme-linked immunosorbent assay (ELISA). RESULTS: Diabetic rats had a significant increase (p<0.03) in apoptotic cell death at half the clinical dose, at the clinical dose, and at double the clinical dose. In vitro, MTT showed a significant decrease (p<0.04) in cellular metabolic activity at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. LDH showed a significant increase (p<0.04) in necrosis at the clinical dose and double the clinical dose compared to control at 48 and 72 hrs. ELISA showed a significant increase (p<0.04) in apoptosis at half the clinical dose, at the clinical dose, and double the clinical dose, compared to control at 48 and 72 hrs. CONCLUSIONS: Anti-VEGF treatment may be potentially detrimental to the retina by decreasing cellular metabolic activity and increasing cytotoxicity of retinal cells. The results provide a cautionary note to monitor both the retina and optic nerve status in patients undergoing frequent injections.

Combination therapy in exudative age-related macular degeneration: visual outcomes following combined treatment with photodynamic therapy and intravitreal bevacizumab.

OBJECTIVE: To measure visual outcomes following combined treatment with photodynamic therapy (PDT) and intravitreal bevacizumab for exudative age-related macular degeneration (AMD). DESIGN: Single-centre, retrospective cohort analysis. PARTICIPANTS: One hundred and seventy-four eyes in 174 patients, representing a consecutive series of all patients with at least 6 months' follow-up after combined treatment with PDT and bevacizumab for exudative AMD. METHODS: Each patient was treated with PDT, followed by intravitreal injection of bevacizumab approximately 30 minutes later. The patients were then followed at 8-12-week intervals. The primary outcome of the study was the mean change in visual acuity (VA) from baseline. RESULTS: One hundred seventy-four eyes in 174 patients completed at least 6 months' follow-up, with a mean duration of 10 months. The mean number of treatments was 3.0 for bevacizumab and 1.4 for PDT. After stabilization, the mean treatment-free interval was 193 days, and 52% of the patients did not require postinduction retreatment. Mean VA improved from baseline at 2, 4, and 6 months of follow-up (p < 0.05). In the subgroup analysis, treatment-naïve patients had more favorable visual outcomes (p < 0.05). CONCLUSIONS: The combination of PDT and intravitreal bevacizumab is an effective therapy for preserving VA in patients with exudative AMD.

Age-related macular degeneration and low-vision rehabilitation: a systematic review.

BACKGROUND: Because of the prevalence and devastating consequences of age-related macular degeneration (AMD), a systematic review devoted to low-vision rehabilitation and AMD seems timely and appropriate. METHODS: Several electronic databases were searched for studies from 1980 to 2006 involving individuals with low vision or visual impairment and rehabilitation interventions. Studies were assessed for quality and level of evidence. RESULTS: The findings indicate that standard low-vision rehabilitation programs, conventional in-clinic assessments, and optical devices are effective ways of managing and living with vision loss. Areas of unmet need include determining which types of orientation and mobility programs and devices are most effective and developing methods of matching assistive technologies with the individual's visual and environmental requirements. INTERPRETATION: Additional randomized controlled trials with similar intervention comparisons and outcome measures are needed to form stronger conclusions for the most effective low-vision rehabilitation interventions for individuals with AMD.

Prospective evaluation of digital non-stereo color fundus photography as a screening tool in age-related macular degeneration.

PURPOSE: To evaluate mydriatic, non-stereo digital color fundus photographs as a screening tool for identifying and classifying exudative age-related macular degeneration (AMD). DESIGN: Prospective case series. METHODS: Digital color fundus photographs were obtained from patients seen in the AMD screening clinic over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs for eligible patients were separated by eye, cataloged, blinded, and randomly labeled before interpretation by an experienced vitreoretinal surgeon. Exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of the fundus photographs in diagnosing, classifying, and managing cases of suspected exudative AMD were then calculated against gold standard clinical examination and fluorescein angiography. RESULTS: A total of 223 images were used from 118 eligible patients. Exact agreement between photographic evaluation and gold standard ranged from 89.2% (presence of pigment epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium geographic atrophy). Positive predictive value ranged from 86.1% (presence of CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1% (presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk dry changes and active exudative changes, overall sensitivity specificity, positive predictive value, and negative predictive value were 82.1%, 79.1%, 70.4%, and 88.0%, respectively. CONCLUSIONS: Digital, non-stereo color fundus photographs are highly sensitive and have high negative predictive value as a screening tool. Very few treatable lesions are missed using telemedicine in age-related macular degeneration.