International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process. DESIGN: Systematic review and Delphi consensus process. PARTICIPANTS: 25 international retinal specialists participated in the Delphi consensus survey. METHODS: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped refine the final classification system. MAIN OUTCOME MEASURES: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration. RESULTS: After screening 18,229 articles, 130 complications were initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses.

A case of recurrent viral retinitis treated with intravitreal antiviral agents in a silicone oil filled eye.

PURPOSE: To report a case of recurrent acute retinal necrosis (ARN) in an eye filled with silicone oil previously complicated by rhegmatogenous retinal detachment (RRD). OBSERVATIONS: A 68-year-old gentlemen with successfully treated herpes simplex virus type 1 (HSV1) ARN complicated by RRD requiring pars plana vitrectomy (PPV) with silicone oil tamponade, presented with a relapse of ARN with silicone oil in situ. Remission of recurrent retinitis was achieved using combined systemic oral and intravitreal antiviral therapy. CONCLUSIONS AND IMPORTANCE: RRD is a significant complication of ARN which may require surgery with silicone oil tamponade. Recurrence of ARN retinitis can be effectively treated with intravitreal Ganciclovir and Foscarnet injections in a silicone oil filled eye with concurrent oral antiviral therapy. Aqueous humour sampling proved useful in the monitoring of disease activity.

Novel application of Deep Anterior Lamellar Keratoplasty for retinal detachment repair in totally opaque cornea secondary to aniridia.

PURPOSE: We present a novel approach for managing retinal detachment in a patient with aniridia related corneal scarring precluding fundal view via a deep anterior lamellar keratoplasty. METHODS: A 30-year-old female patient who had bilaterally opaque cornea, due to advanced aniridia related keratopathy presented with, experiencing flashing of light in her right eye. Examination of the retinal fundus was not possible due to the dense corneal scarring and underlying cataract. A superior bullous macula off retinal detachment was diagnosed on ultrasonography. Visual acuity at presentation was hand motions. The corneal scarring extended to the mid to deep stroma. We performed a deep anterior lamellar dissection of the opacified corneal stroma, that allowed clear visualisation of a dense cataract. The cataract was removed by phacoemulsification and IOL inserted. This allowed to proceed with repair of retinal detachment, through pars plana approach. The surgery was completed by a donor deep lamellar keratoplasty. RESULTS: This achieved a good fundal view to proceed with phacovitrectomy visualised through the residual corneal layers. Uneventful pars plana vitrectomy, cryotherapy and SF6 gas were performed to reattach the retina. Post-operatively the graft remains clear at 6 months with a visual acuity of 20/160 in the right eye, a level of vision the patient had not experienced for decades. CONCLUSION: Deep anterior lamellar keratoplasty offered an alternative to temporary keratoprosthesis to achieve a clear view of the retinal fundus and perform pars plana vitrectomy and repair of the retinal detachment.

Safety and effectiveness of pre-emptive diabetic vitrectomy in patients with severe, non-fibrotic retinal neovascularisation despite panretinal photocoagulation.

OBJECTIVES: To investigate the safety and effectiveness of pre-emptive vitrectomy in eyes with severe non-fibrotic proliferative diabetic retinopathy. METHODS: A multi-centre, retrospective, observational study. Pre-emptive vitrectomy was performed in non-fibrotic diabetic eyes with a visual acuity (VA) of 20/50 or better, where there was extensive persistent neovascularisation despite prior panretinal photocoagulation, and where the fellow eye had established sight loss despite vitrectomy for tractional complications. The primary outcome measure was the VA at last visit. RESULTS: Twenty patients were included. The mean age was 39 ± 14 years. Fifteen patients were Type 1 diabetic. The median baseline VA was 20/30 and remained stable at 20/28 at last visit (median follow-up period: 24 months). Eight eyes (40.0%) developed post-operative vitreous cavity haemorrhage; 4 of which required a vitreous cavity washout procedure. There were no post-operative retinal detachments. The index eye remained the significantly better eye at all time points bar one month post-surgery. Regression of retinopathy grading was observed in all eyes. CONCLUSION: In this pilot study, we found no sight loss with pre-emptive diabetic vitrectomy. Better eye status was maintained in this high-risk group. Further study with larger number of patients and longer-term follow-up is indicated.

Paclitaxel may be a risk factor for retinal phototoxicity.

PURPOSE: To report the first case, to our knowledge, of suspected paclitaxel induced phototoxic maculopathy following vitrectomy surgery. OBSERVATIONS: A 62-year-old phakic female receiving paclitaxel therapy for ovarian carcinoma presented with a best corrected visual acuity (BCVA) of 20/40 OD with an epiretinal membrane (ERM) and lamellar macular hole on spectral domain optical coherence tomography (SD-OCT). The patient underwent an uneventful pars plana vitrectomy with ERM peel using standard illumination and vitrectomy settings. Membrane Blue Dual (DORC, Netherlands) was used to stain the ERM. Two weeks post-operatively, the patient presented with a reduced BCVA of 20/200 in the operated eye. Fluorescein and indocyanine green angiography revealed right sided patchy hypofluorescence and hyperfluorescence secondary to retinal pigment epithelium changes with intact choroidal and retinal vasculature. SD-OCT and fundoscopy showed right sided loss of ellipsoid layer, increased reflectivity within the retinal pigmented epithelium and subretinal fibrosis without cystoid macular edema. Four months post-operatively her vision had stabilized to 20/160; unfortunately, the patient was palliated a month later due to ovarian carcinoma progression. CONCLUSIONS: A number of drugs are known to increase photosensitivity to solar and artificial forms of radiation. Paclitaxel use has been widely reported to cause dermatological photosensitivity. We report a case of suspected paclitaxel induced phototoxic maculopathy following endoillumination during vitrectomy surgery.

Heavy silicone oil tamponade: a multicentre experience.

OBJECTIVE: To report multicentred use of the heavy silicone oil Densiron 68 for anatomical reattachment following rhegmatogenous retinal detachment (RRD) repair and its associated complications. METHODS AND ANALYSIS: Patients from seven vitreoretinal units within the UK that underwent RRD repair with Densiron 68 between January 2015 and December 2019 were identified. Primary outcome measures were primary and final reattachment rate, retained Densiron and failure rate. Secondary outcome measures were duration of tamponade, final visual acuity (VA) and complications of heavy silicone oil. RESULTS: 134 eyes of 134 patients were involved in the study. Primary surgical success was achieved in 48.5%, while a final reattachment rate of 73.4% was observed. The mean duration of Densiron 68 tamponade was 139.5 days. Mean final VA was 1.01 (range 0-2.9). 8 eyes (6.0%) required long-term topical steroids for anterior uveitis, whereas none of the eyes required long-term pressure-lowering treatment. Emulsification rate was 10.7% (6 eyes). CONCLUSION: This is the largest real-world study on Densiron 68 in the UK. Densiron 68 facilitates tamponade of inferior retinal pathology and may be considered as an option for tamponade of inferior retinal pathologies.

Cognitive visual impairment with good visual acuity in children with posterior periventricular white matter injury: a series of 7 cases.

BACKGROUND: We describe a series of term and preterm children with occipito-parietal periventricular white matter abnormalities on magnetic resonance imaging (MRI) who manifest common clinical features of cognitive visual dysfunction. We also describe a strategy for taking clinical history that highlights the symptom complex and assists with management. PATIENTS AND METHODS: A retrospective observational case series study of seven children with cognitive visual difficulties despite good (20/32 or better) visual acuities and MRI findings of periventricular white matter pathology in the territory subserving visual function. Structured history taking was used to identify and characterize the visual difficulties. Objective clinical findings (visual acuity, color vision, stereoacuity, visual fields, ocular motility, refraction, and fundoscopy) were recorded. RESULTS: Seven children with visual acuities of 20/32 (0.200 logMAR) or better had symptoms of cognitive visual difficulties consistent with dorsal stream dysfunction. Four had strabismus of different types and were identified on the basis of parental concern expressed at the ocular motility clinic. The other three children presented to the general ophthalmology clinic. All seven children had various degrees of focal periventricular white matter pathology in a similar distribution on neuroimaging. CONCLUSIONS: Children born prematurely are susceptible to periventricular white matter pathology. Such pathology can also occur in children born at term. This case series demonstrates that cognitive visual impairment due to periventricular white matter injury can occur despite good central visual function. A range of strategies to help affected children is described.

Risk factors for visual impairment in patients with sickle cell disease in London.

PURPOSE: Dramatically improved health care in recent years has increased the life expectancy of patients with sickle cell disease (SCD) as well as the prognosis for its ocular complications. We sought to identify risk factors for visual impairment in patients with SCD in London 4 decades after Goldberg's seminal studies. METHODS: Patients 16 years and older with SCD (genotypes HbSS, HbSC, HbSß-thalassemia) attending hematology and ophthalmology services were offered ocular examination. Retinopathy was graded according to the Goldberg classification. Visual impairment was defined as corrected distance visual acuity of 20/40 or poorer. RESULTS: In total, 182 eyes of 182 patients (mean ± SD age, 37.2 ± 12.8 years; female, 65.9%) were included. Women were significantly older than men (mean ± SD age, 38.8 ± 13.1 vs 34.2 ± 11.8 years; p = 0.0174). There was no difference in mean age of each genotype group (p>0.15). Risk factors for sight-threatening proliferative sickle retinopathy (PSR) were age over 35 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.05-3.89; p = 0.0359) and HbSC genotype (OR 4.06; 95% CI 2.07-7.98; p<0.0001). Although visual impairment was related to the presence of sight-threatening PSR (OR 7.23; 95% CI 1.50-35.0; p = 0.0138), it was not related to hemoglobin genotype (p>0.50). CONCLUSIONS: We present the largest study of ocular findings in SCD in the United Kingdom. Sight-threatening PSR is a risk factor for visual impairment, but hemoglobin genotype status is not.

Long-term study of vascular perfusion effects following arteriovenous sheathotomy for branch retinal vein occlusion.

PURPOSE: To evaluate the perfusion effects and long-term visual outcome of pars plana vitrectomy (PPV) combined with arteriovenous sheathotomy (AVS) with or without triamcinolone for nonischaemic branch retinal vein occlusion (NI-BRVO). METHODS: Prospective, interventional case series of eight patients with NI-BRVO and haemorrhagic macular oedema. Patients underwent PPV and AVS (n = 5), or PPV, AVS and intravitreal triamcinolone (IVT, n = 3). A masked grading technique assessed fundus photographs and fluorescein angiography (FFA) following surgery. Scanning laser ophthalmoscopy/optical coherence tomography (SLO/OCT) evaluated macular oedema and outer retinal architecture. Main outcomes examined included visual acuity (VA), retinal reperfusion, collateral vessel regression, vascular dilatation, cystoid macular oedema (CMO), and ocular neovascularization. RESULTS: Seven of eight patients underwent uncomplicated surgery, with increased intraretinal perfusion and reduced engorgement of distal retinal veins. The mean pre-logMAR VA was 0.8 (SD 0.17) and did not improve significantly after surgery (post-logMAR 0.6, SD 0.38; p = 0.11, paired t-test). SLO/OCT showed persistent CMO in four patients, and subfoveal thinning of the photoreceptor layer. Collateral vessels disappeared at the blockage site post-AVS in 7/8 eyes, and this was associated with improved retinal perfusion. Six of eight patients developed epiretinal membrane. No patients developed ocular neovascularization. The average follow-up was 34.5 months. CONCLUSIONS: PPV with AVS is a safe procedure, and adjunctive IVT had no additional effects on vascular perfusion. Successful decompressive surgery was followed by disappearance of collateral vessels at the BRVO blockage site and was a clinical marker for intravascular reperfusion. Long-term epiretinal gliosis and subfoveal photoreceptor atrophy limited functional and visual recovery.