Update on Retinal Drug Safety: Proceedings of the ASRS ReST Committee Webinar Part 1.

Purpose: To review the first Research and Safety in Therapeutics (ReST) Committee webinar and summarize the most current recommendations regarding diagnosis and management. Methods: The ReST Committee is comprised of members of the American Society of Retina Surgeons (ASRS). At regular internal meetings, safety issue reports from the website are reviewed. A webinar series was started in 2021 to update members on multiple relevant potential safety events. Results: Topics reviewed in the webinar included pentosan polysulfate sodium (Elmiron) maculopathy, intraocular pressure elevation reported with the aflibercept prefilled syringe (PFS), and brolucizumab-associated inflammation with occlusive retinal vasculitis. Retinal toxicity related to intraoperative medications was reviewed, including hemorrhagic occlusive retinal vasculitis after intraocular vancomycin, dilution errors with intravitreal aminoglycosides, inadvertent overdoses of cefuroxime after cataract surgery, and toxic posterior segment syndrome after dropless cataract surgery using compounded triamcinolone-moxifloxacin. Indocyanine green toxicity has been reported after its use as an adjuvant during macular hole surgery. Conclusions: The past decade has seen advances in retinal pharmaceuticals and drug-delivery devices. The ASRS ReST Committee collects data from its website reporting system to inform members about up-to-date pharmaceutical and device safety concerns. Recently, a webinar was used to inform members of pigmentary maculopathy associated with pentosan polysulfate sodium, safety regarding the aflibercept PFS, intraocular inflammation and occlusive retinal vasculitis secondary to brolucizumab, and retinal toxicity from intraoperative ocular medications.

Optical coherence tomography imaging of the peripheral retina.

This review critically assesses the applicability of retinal periphery imaging technology, scrutinizing its practical limitations and potential advancements within ophthalmology. It underscores the significant costs and the need to evaluate the clinical utility of optical coherence tomography (OCT) and OCT angiography devices. It emphasizes how clinicians should consider their practice-specific use-cases while investing in devices with capabilities like ultra-widefield OCT, autofluorescence imaging, and angiography. The paper also highlights the challenges associated with image acquisition, such as artifact management and patient cooperation for extended fixation periods. This review outlines the utility of these modalities in various retinal pathologies, as well as their contribution to telemedicine and personalized care, facilitated by artificial intelligence for improved image processing, quantification, and interpretation. These techniques potentially offer a more comprehensive understanding of peripheral retinal conditions and associated pathologies, thus influencing clinical decision-making, particularly in remote regions with limited specialist access.

OCTA: Essential or Gimmick?

This commentary article delves into the transformative role of optical coherence tomography angiography (OCTA) in diagnosing and managing a wide array of eye conditions, including diabetic retinopathy, age-related macular degeneration, retinal vein occlusions, and white dot syndromes. Developed in 2005, OCTA has emerged as a non-invasive, high-resolution imaging technique that offers advantages over traditional fluorescein angiography (FA), providing quicker and safer monitoring of ocular conditions with similar diagnostic accuracy. In diabetic retinopathy, OCTA has been instrumental in early identification of retinal changes, offering quantifiable metrics including perfused capillary density (PCD) for assessing vascular alterations. For age-related macular degeneration (AMD), OCTA has deepened our understanding of non-exudative neovascular AMD, allowing for more effective monitoring and potential earlier initiation of treatment. In cases of retinal vein occlusions, OCTA can reveal specific microvascular features and allow for depth-resolved measurements of the foveal avascular zone, providing significant prognostic implications. OCTA has also been invaluable in studying rare white dot syndromes, enabling nuanced differentiation between conditions that often present similarly. Emerging research also suggests that OCTA can have potential utility in neurodegenerative diseases like Alzheimer's, where retinal vascular patterns could offer diagnostic insights. While OCTA is revolutionizing ophthalmic care, further clinical trials and standardization are needed for its broader adoption into clinical practice.

Novel features of degenerative retinoschisis identified using ultra-widefield multicolor channels: A review of 139 eyes.

BACKGROUND/OBJECTIVE: To utilize ultra-widefield multimodal imaging (Optos PLC) to describe novel findings in degenerative retinoschisis. METHODS: This retrospective, non-comparative case series of degenerative retinoschisis received a waiver of consent from Advarra IRB, Protocol 00066379. Initial ultra-widefield pseudocolour, colour-separated, autofluorescence, and peripheral OCT imaging were analysed for characterizing features. RESULTS: In total, 139 eyes were included. A hyporeflective reticular pattern associated with retinoschisis was seen on pseudocolour images in 39% of cases, but visible in 53% on green-separated images. Fine hyper-reflective foci were observed in 49%. In 27%, retinoschisis was confirmed with OCT. CONCLUSIONS: Ultra-widefield pseudocolour and green-separated images are valuable for the diagnosis and characterization of degenerative retinoschisis. The findings described may prompt the evaluation of subtle retinoschisis with peripheral OCT.

Anti-VEGF and steroid combination therapy relative to anti-VEGF mono therapy for the treatment of refractory DME: A systematic review of efficacy and meta-analysis of safety.

The aim of the study was to determine the efficacy and safety of combined anti-VEGF and steroid therapy in treatment refractory DME patients. We conducted a systematic review and meta-analysis of peer-reviewed articles reporting on visual, anatomical and adverse outcomes to compare the efficacy and safety of combined intravitreal anti-VEGF/steroids versus anti-VEGF monotherapy for refractory DME. Seven studies (4 RCTs and 3 observational studies) reporting on 452 eyes were included. Our systematic review showed that combination therapy is significantly more effective for anatomical outcomes in the treatment of resistant DME compared to anti-VEGF monotherapy in six studies. Two studies found that addition of intravitreal steroids promoted faster visual improvement, but not significantly better final visual outcomes compared to anti-VEGF monotherapy. Combination therapy was associated with a higher incidence of IOP-related adverse events (RR = 0.10, 95% CI = [0.02, 0.42], p = 0.002) and cataract-related adverse events (RR = 0.10, 95% CI = [0.01, 0.71], p = 0.02). Our systematic review and meta-analysis of seven studies and 452 eyes revealed that combination therapy of anti-VEGF and steroid intravitreal drugs in the management of treatment refractory DME resulted in superior anatomical outcomes in all but one study. Combination therapy led to superior short-term visual outcomes in two studies, while others reported no difference between treatment groups. Meta-analysis revealed that combination therapy was associated with more adverse events. Future research should provide guidance on the standard definitions for treatment resistance and therapeutic alternatives for DME patients with sub-optimal response to anti-VEGF treatment.

Risk for Surgical Team Hearing Loss With Vitrectomy.

Purpose: To assess sound-level exposure during vitrectomy using 3 of the most common commercially available machines. Methods: This noninterventional cross-sectional study examined sound emission from the Constellation, Stellaris, and EVA vitrector systems. For each machine, a noise dosimeter was used to measure the sound-level exposure of the surgeon during 3 surgical cases in which vitrectomy was performed. Sound levels associated with progressively increasing cut rates and vacuum pressures were also measured. Finally, sound measurements were taken during the use of various additional functions of each machine, including diathermy, laser, and extrusion. Sound levels were compared with occupational health guidelines in Canada and the United States. Results: The maximum sound level recorded during vitrectomy surgery was 88.2 dBA. The mean sound level during vitrectomy surgical cases ranged from 58.5 to 66.8 dBA. A strong positive linear correlation was found between the cut rate and sound level (r = 0.88-0.98) and the vacuum pressure and sound level (r = 0.83-0.97). This relationship was consistent across the 3 vitrector systems (P < .001). Conclusions: Noise exposure during vitrectomy procedures was acceptable but may be sufficient for surgical team activity interference, as described by World Health Organization recommendations. A strong correlation was found between the cut rate and noise exposure. If cut rates continue to increase, attention should be given to ensure that the resulting noise exposure does not threaten the hearing of vitreoretinal surgeons and the operating room staff.

UTILIZATION OF PREOPERATIVE MIDPERIPHERAL OPTICAL COHERENCE TOMOGRAPHY FOR TAILORED SURGICAL MANAGEMENT OF PROLIFERATIVE VITREORETINOPATHY.

PURPOSE: The purpose of this study was to report on the use of preoperative spectral domain optical coherence tomography to assess retinal pathology and guide the surgical approach to proliferative vitreoretinopathy. METHODS: A case report was discussed. RESULTS: A 70-year-old man developed proliferative vitreoretinopathy after surgical repair of a macula-off rhegmatogenous retinal detachment. In preparation for further surgery, inferior preretinal fibrosis and membranes were identified on preoperative optical coherence tomography. The patient underwent successful vitrectomy with peeling of the membranes resulting in markedly improved visual acuity. CONCLUSION: Widely available spectral domain optical coherence tomography can be used preoperatively to image the midperipheral retina and guide surgical decision-making in the management of proliferative vitreoretinopathy.

Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for nAMD treatment.

TOPIC: This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: We conducted systematic searches from January 2003 to August 2022 on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials. We included studies reporting changes in early treatment diabetic retinopathy study-measured best-corrected visual acuity (BCVA), number of patients who lost or gained more than 15 letters in BCVA from baseline, changes in retinal thickness and adverse events between treatment arms. The following studies were excluded: studies that did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF agents with laser or steroid injections, sham injections as a control comparator, studies without English full texts and non-comparative, observational study design. RESULTS: Five studies reported on four randomised controlled trials (RCTs) and 1544 eyes at baseline were included in this systematic review and meta-analysis. The studies in our systematic review found no significant differences between reference ranibizumab and ranibizumab biosimilar medications (FYB201, SB11, RanizuRel and Lupin's ranibizumab) for visual and anatomical outcomes. No significant differences were detected between biosimilar and reference ranibizumab for treatment emergent adverse events (risk ratio, RR 1.06, 95% CI (0.91 to 1.23), p=0.45, I2=52%) or IOP-related adverse events with significant heterogeneity (RR 2.59, 95% CI (0.11 to 62.25), p=0.56, I2=76%). CONCLUSION: This systematic review of four RCTs demonstrated no significant difference in visual outcomes, retinal thickness outcomes, as well as meta-analysis of adverse events between biosimilar and reference ranibizumab therapies for nAMD treatment.

Practical applications of vitreous imaging for the treatment of vitreous opacities with YAG vitreolysis.

PURPOSE: To demonstrate the methodology and efficacy of using scanning laser ophthalmoscopy (SLO) and dynamic optical coherence tomography (OCT) to identify and treat symptomatic vitreous floaters using yttrium-aluminum garnet laser vitreolysis (YLV). METHODS: This is a case series highlighted from a cross sectional retrospective study conducted at the Vitreous Retina Macula Specialists of Toronto. Forty eyes from thirty-five patients were treated with YLV between November 2018 and December 2020 for symptomatic floaters and imaged with SLO and dynamic OCT. Patients were re-treated with YLV if they reported ongoing significant vision symptoms during follow-up which correlated to visible opacities on exam and or imaging. Three cases will be highlighted to present the practical applications of SLO and dynamic OCT imaging for YLV treatment. RESULTS: Forty treated eyes were enrolled in this study, with twenty-six eyes (65%) requiring at least one repeat YLV treatment following the first treatment due to ongoing symptomatic floaters. Following the first YLV, there was a significant improvement in overall mean best corrected visual acuity compared to before treatment (0.11 ± 0.20 LogMAR units vs. 0.14 ± 0.20 LogMAR units, p = 0.02 (paired t test)). Case 1 demonstrates a dense, solitary vitreous opacity that has been localized with dynamic OCT imaging to track its movements and retinal shadowing with the patient's eye movements. Case 2 shows the utility of adjusting the fixation target to monitor the movement of vitreous opacities in real-time. Case 3 exhibits an association between decreased symptom burden and vitreous opacity density after YLV. CONCLUSION: Image-guided YLV facilitates the localization and confirmation of vitreous opacities. SLO and dynamic OCT of the vitreous can provide a real-time evaluation of floater size, movement, and morphology, to help clinicians target treatment and monitoring of symptomatic floaters.

The relationship of diabetic retinopathy severity scales with frequency and surface area of diabetic retinopathy lesions.

PURPOSE: To assess the relationship between qualitative diabetic retinopathy (DR) scales with the precise numbers and surface area of DR lesions within the Early Treatment Diabetic Retinopathy Study (ETDRS) standard seven field (S7F) region on ultrawide-field (UWF) color fundus images. METHODS: In this study, we collected UWF images from adult patients with diabetes. Poor-quality images and eyes with any pathology precluding assessment of DR severity were excluded. The DR lesions were manually segmented. DR severity was graded according to the International Clinical Diabetic Retinopathy (ICDR) and AA protocol by two masked graders within the ETDRS S7F. These lesions' numbers and surface area were computed and correlated against the DR scores using the Kruskal-Wallis H test. Cohen's Kappa was performed to determine the agreement between two graders. RESULTS: One thousand five hundred and twenty eyes of 869 patients (294 females, 756 right eyes) with a mean age of 58.7 years were included. 47.4% were graded as no DR, 2.2% as mild non-proliferative DR (NPDR), 24.0% as moderate NPDR, 6.3% as severe NPDR, and 20.1% as proliferative DR (PDR). The area and number of DR lesions generally increased as the ICDR level increased up to severe NPDR, but decreased from severe NPDR to PDR. There was perfect intergrader agreement on the DR severity. CONCLUSION: A quantitative approach reveals that DR lesions' number and area generally correlate with ICDR-based categorical DR severity levels with an increasing trend in the number and area of DR lesions from mild to severe NPDR and a decrease from severe NPDR to PDR.

Factors contributing to the carbon footprint of cataract surgery.

The healthcare sector is a significant greenhouse gas emitter. Cataract surgery is a procedure that results in a large amount of carbon dioxide (CO2) emissions. We sought to review the literature for factors contributing to the carbon footprint of this procedure. The literature, although limited, varies greatly by region. The carbon footprint of cataract surgery ranged from approximately 6 kg CO2 equivalents in a center in India to 181.9 kg CO2 equivalents in a center in the United Kingdom. Factors contributing to the carbon footprint of cataract surgery included the procurement of materials, energy use, and the emissions associated with travel. Factors facilitating a lower carbon footprint include the reuse of surgical materials and more efficient autoclave settings. Potential areas for improvement to consider include the reduction in packaging material, the reuse of materials, and potentially reducing travel emissions by performing simultaneous bilateral cataract surgery.

SPONTANEOUS RESOLUTION OF RETINOSCHISIS IN THE SETTING OF NARROW-ANGLE GLAUCOMA: A CASE REPORT.

PURPOSE: To present a rare case of retinoschisis in the setting of narrow-angle glaucoma that demonstrated spontaneous resolution with conservative management. METHODS: Case report presentation from the Vitreous Retina Macula Specialists of Toronto in December 2020. RESULTS: A 65-year-old woman with previous bilateral laser peripheral iridotomies for narrow-angle glaucoma was referred to a tertiary retina clinic for the assessment of query macular edema in the left eye. The patient presented with a blunted foveal reflex in the left eye, and optical coherence tomography imaging demonstrated diffuse retinoschisis of outer retinal layers in the peripapillary region and nasal macula. The patient elected for conservative management, and by 10-month follow-up, her retinoschisis resolved spontaneously. CONCLUSION: Only seven cases of retinoschisis in the setting of narrow-angle glaucoma have been identified in the literature. This is the first case in this setting to demonstrate spontaneous resolution with conservative management. Although laser peripheral iridotomies have been shown to resolve retinoschisis in narrow-angle glaucoma patients, clinicians should be aware of a conservative management approach to yield a positive improvement in retinal integrity.

Multimodal Imaging Study of Patients With Vitamin A Deficiency Retinopathy.

OBJECTIVES: To describe multimodal imaging findings of vitamin A deficiency retinopathy. METHODS: A retrospective study of patients with serum retinol < 0.3 mg/L. Fundus color photos, spectral domain-optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) were reviewed and, when available, electrophysiological tests were analyzed. RESULTS: Forty-five eyes (63.9 ± 15.7 years) were included. Ultra-widefield fundus photography showed drusen-like deposits (53.3%) and macular retinal pigment epithelium (RPE) mottling (40%). The deposits were hypoautofluorescent, and a perifoveal hyperautofluorescent ring was present in 8.9%. By SD-OCT, the ellipsoid zone had an irregular appearance (100%) and conical deposits anterior to the RPE (33.3%). Electroretinogram (ERG) (66.7%) showed a decrease in b-wave in the scotopic registers, and microperimetry (4.4%) showed decreased foveal sensitivity. After vitamin A supplementation, SD-OCT and FAF showed resolution of all findings. Forty percent of eyes had restoration of the scotopic registers in ERG and improved macular sensitivity by microperimetry (4.4%). CONCLUSIONS: Vitamin A deficiency causes a mild cone dysfunction in addition to the more severe absent rod response. [Ophthalmic Surg Lasers Imaging Retina 2023;54:330-336.].

Comparison of diabetic retinopathy severity grading on ETDRS 7-field versus ultrawide-field assessment.

OBJECTIVES: To compare the diabetic retinopathy (DR) severity level determined when considering only the ETDRS 7-field region versus the entire ultrawidefield (UWF) image. METHODS: In this retrospective, cross-sectional study, UWF pseudocolor images were graded on the Eyenuk image viewing, grading, and annotation platform for the severity of DR considering only the regions within the ETDRS 7-fields as well as the entire UWF image using two different protocols: 1) the simple International Classification of Diabetic Retinopathy (ICDR) scale and 2) the more complex DRCR.net Protocol AA grading scale. RESULTS: A total of 250 eyes from 157 patients were included in this analysis. Six eyes (2.4%) demonstrated a discrepancy in severity level between the ETDRS 7-field region and the entire UWF image when using the ICDR classification system. The discrepancies were due to the presence of lesions [intraretinal haemorrhage (n = 2), neovascular disease (n = 4)] in the peripheral fields which were not identified in the ETDRS 7-fields. Fourteen eyes (5.6%) had a discrepancy in severity level between the ETDRS 7-field region and the entire UWF image when using the ETDRS DRSS Protocol AA grading scale. The discrepancies were due to the presence of a higher level of disease [intraretinal haemorrhage (n = 4), neovascularization (n = 4), preretinal haemorrhage (n = 2), scatter laser scars (n = 4)] in the peripheral fields. CONCLUSION: Although considering regions outside of the ETDRS 7-fields altered the DR severity level assessment in <5% of cases in this cohort, significant and potentially vision-threatening lesions including neovascularization and preretinal haemorrhage were identified in these peripheral regions. This highlights the importance of evaluating the entire UWF region when assessing patients with diabetic retinopathy.

Emerging Treatment Options for Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is characterized as a chronic, multifactorial disease and is the leading cause of irreversible blindness. Advanced AMD is classified as neovascular (wet) AMD and non-neovascular (dry) AMD. Dry AMD can progress to a more advanced form that manifests as geographic atrophy (GA), which significantly threatens vision, leading to progressive and irreversible loss of visual function. There are currently no approved therapeutics commercially available for GA patients. However, data from various clinical trials have demonstrated favorable results with significant reduction in GA lesion growth. This review furthers the understanding of the pathophysiology of GA, as well as current clinical trial data on investigational therapeutics.

Anesthesia for ophthalmic surgery: an educational review.

PURPOSE: Selecting an anesthetic agent for ophthalmic surgery has crucial implications for the surgeon, anesthesiologist, and patient. This educational review explores the common classes of anesthesia used in ophthalmology. Additionally, we discuss the considerations unique to cataract, glaucoma, strabismus, orbital, oculoplastic, and ocular trauma surgeries. METHODS: A comprehensive Embase search was performed using combinations of the subject headings "anesthesia", "eye surgery", "ophthalmology" and "cataract extraction", "glaucoma", "strabismus", "vitreoretinal surgery", "retina surgery", "eye injury", and "eyelid reconstruction". RESULTS: Topical anesthetics are the most commonly used form of ocular anesthesia, used in both an office and surgical setting, and carry a minimal side effect profile. Notably, topical anesthetics offer analgesia, but do not provide akinesia or amnesia. Regional blocks, such as are sub-Tenon's, peribulbar, and retrobulbar blocks, are used when akinesia is required in addition to analgesia. Recently, sub-Tenon's blocks have recently gained popularity due to their improved safety profile compared to other regional blocks. General anesthesia is considered for long, complex surgery, surgery in patients with multiple comorbidities, surgery in young pediatric patients, or surgery in patients intolerant to local or regional anesthetic. CONCLUSION: Anesthetizing the eye has rapidly evolved in recent years, supporting the safety, efficacy and comfort of ocular surgery. Since there are many viable options of anesthetics available for ophthalmic surgery, a robust understanding of the patients needs, the skill of the surgical team, and surgery-specific factors ought to be considered when creating an anesthetic plan for surgery.