ASSOCIATION OF INTRAVENOUS FLUORESCEIN ANGIOGRAPHY AND ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Case Series.

PURPOSE: To our knowledge, we present the first case series investigating the relationship between adaptive optics (AO) imaging and intravenous fluorescein angiography (IVFA) parameters in patients with diabetic retinopathy. METHODS: Consecutive patients with diabetic retinopathy older than age 18 years presenting to a single center in Toronto, Canada, from 2020 to 2021 were recruited. Adaptive optics was performed with the RTX1 camera (Imagine Eyes, Orsay, France) at retinal eccentricities of 2° and 4°. Intravenous fluorescein angiography was assessed with the artificial intelligence-based RETICAD system to extract blood flow, perfusion, and blood-retinal-barrier (BRB) permeability at the same retinal locations. Correlations between AO and IVFA parameters were calculated using Pearson's correlation coefficient. RESULTS: Across nine cases, a significant positive correlation existed between photoreceptor spacing on AO and BRB permeability (r = 0.303, P = 0.027), as well as perfusion (r = 0.272, P = 0.049) on IVFA. When stratified by location, a significant positive correlation between photoreceptor dispersion and both BRB permeability and perfusion (r = 0.770, P = 0.043; r = 0.846, P = 0.034, respectively) was observed. Cone density was also negatively correlated with BRB permeability (r = -0.819, P = 0.046). CONCLUSION: Photoreceptor spacing on AO was significantly correlated with BRB permeability and perfusion on IVFA in patients with diabetic retinopathy. Future studies with larger sample sizes are needed to understand the relationship between AO and IVFA parameters in diverse patient populations.

ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Cohort Study.

PURPOSE: To investigate the correlation between diabetic retinopathy (DR) severity and microscopic retinal and vascular alterations using adaptive optics imaging. METHODS: In this single-center, prospective cohort study, adult participants with healthy eyes or DR underwent adaptive optics imaging. Participants were classified into control/mild nonproliferative DR, moderate/severe nonproliferative DR, and proliferative DR. Adaptive optics imaging using the RTX1 camera was obtained from 48 participants (87 eyes) for photoreceptor data and from 36 participants (62 eyes) for vascular data. RESULTS: Photoreceptor parameters significantly differed between DR groups at 2° and 4° of retinal eccentricity. Wall-to-lumen ratio varied significantly at 2° eccentricity, while other vascular parameters remained nonsignificant. Cone density and dispersion were the strongest predictors for DR severity ( P < 0.001) in multivariable generalized estimating equation modeling, while other vascular parameters remained nonsignificant between DR severity groups. All photoreceptor parameters showed significant correlations with visual acuity overall and across most DR severity groups. CONCLUSION: To date, this is one of the largest studies evaluating the use of adaptive optics imaging in DR. Adaptive optics imaging was demonstrated to differentiate between various levels of disease severity in DR. These results support the potential role in diagnostic and therapeutic microstructural evaluation in research and clinical practice.

Phosphatidylinositol 3-Phosphate Mediates the Establishment of Infectious Bursal Disease Virus Replication Complexes in Association with Early Endosomes.

Infectious bursal disease virus (IBDV) is the archetypal member of the family Birnaviridae and the etiological agent of Gumboro disease, a highly contagious immunosuppressive infection of concern to the global poultry sector for its adverse health effects in chicks. Unlike most double-stranded RNA (dsRNA) viruses, which enclose their genomes within specialized cores throughout their viral replication cycle, birnaviruses organize their bisegmented dsRNA genome in ribonucleoprotein (RNP) structures. Recently, we demonstrated that IBDV exploits endosomal membranes for replication. The establishment of IBDV replication machinery on the cytosolic leaflet of endosomal compartments is mediated by the viral protein VP3 and its intrinsic ability to target endosomes. In this study, we identified the early endosomal phosphatidylinositol 3-phosphate [PtdIns(3)P] as a key host factor of VP3 association with endosomal membranes and consequent establishment of IBDV replication complexes in early endosomes. Indeed, our data reveal a crucial role for PtdIns(3)P in IBDV replication. Overall, our findings provide new insights into the replicative strategy of birnaviruses and strongly suggest that it resembles those of positive-strand RNA (+ssRNA) viruses, which replicate in association with host membranes. Furthermore, our findings support the role of birnaviruses as evolutionary intermediaries between +ssRNA and dsRNA viruses and, importantly, demonstrate a novel role for PtdIns(3)P in the replication of a dsRNA virus.IMPORTANCEInfectious bursal disease virus (IBDV) infects chicks and is the causative agent of Gumboro disease. During IBDV outbreaks in recent decades, the emergence of very virulent variants and the lack of effective prevention/treatment strategies to fight this disease have had devastating consequences for the poultry industry. IBDV belongs to the peculiar family Birnaviridae Unlike most dsRNA viruses, birnaviruses organize their genomes in ribonucleoprotein complexes and replicate in a core-independent manner. We recently demonstrated that IBDV exploits host cell endosomes as platforms for viral replication, a process that depends on the VP3 viral protein. In this study, we delved deeper into the molecular characterization of IBDV-endosome association and investigated the role of host cell phosphatidylinositide lipids in VP3 protein localization and IBDV infection. Together, our findings demonstrate that PtdIns(3)P serves as a scaffold for the association of VP3 to endosomes and reveal its essential role for IBDV replication.

GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.

PURPOSE: Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration. METHODS: Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy. RESULTS: Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21-1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen. CONCLUSION: We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.

Pars plana vitrectomy versus intravitreal antibiotics for endophthalmitis management following intravitreal anti-VEGF agents: A meta-analysis.

In this meta-analysis, we aim to compare the efficacy and safety of pars plana vitrectomy (PPV) versus tap-and-inject (TAI) of intravitreal antibiotics for the management of endophthalmitis secondary to intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central (January 2005-October 2022). The primary analysis compared initial PPV versus TAI and the secondary analysis examined the efficacy and safety of TAI alone compared to TAI followed by PPV. The quality of non-randomized observational studies was assessed using the Newcastle-Ottawa Scale. The quality of the evidence was assessed for each outcome. A random effects meta-analysis was performed. Weighted mean differences (WMDs) with 95% confidence intervals were reported. Of the 7474 screened studies, nine studies reporting on 153 eyes were included. The change in mean best corrected visual acuity (BCVA) between endophthalmitis presentation and last follow-up did not significantly differ between the initial TAI versus PPV groups (WMD = 0.05 units; 95% CI -0.12 to 0.22; p = 0.59; heterogeneity p = 0.41). The difference in pre- to post-treatment mean BCVA did not significantly differ between eyes that received TAI alone or TAI followed by PPV (WMD = 0.04 units; 95% CI -0.42 to 0.51; p = 0.85; heterogeneity p = 0.74). While the meta-analysis revealed no significant difference in the change in BCVA between PPV and TAI to treat endophthalmitis secondary to anti-VEGF agents, the quality of evidence was low with potential for confounding and selection bias. Further well-designed studies in this setting are needed.

Comparison of the Photoreceptor Mosaic Before and After Macular Hole Surgery with High Resolution Adaptive Optics Imaging.

PURPOSE: To assess the photoreceptor mosaic in patients with idiopathic full thickness macular hole (MH) before and after pars plana vitrectomy (PPV) with adaptive optics enhanced retinal imaging (AO). DESIGN: Prospective case series. METHODS: Prospective cohort study of patients who presented at the Kensington Eye Institute, Toronto, Canada with a diagnosis of macular hole treated with PPV. EXCLUSION CRITERIA: secondary MH, high myopia (axial length >26.5 mm), media opacity precluding OCT or AO imaging, previous intraocular surgery except for cataract extraction. Imaging using an AO fundus camera (Imagine Eyes, RTX1) was performed preoperatively and 3-months following successful MH repair in both eyes. Cone density (CD), regularity, dispersion, regularity, dispersion, and spacing were measured at 2° and 4° of eccentricity in 4 quadrants (superior, inferior, nasal, and temporal) with pre- and postoperative values compared. RESULTS: We included 18 eyes of 9 patients. At 2° there was significant reduction in CD and increase in spacing and dispersion and a non-significant change in regularity post-operatively. Comparison between preoperative and postoperative measurements at 2° mean (Standard Error= SE) were: CD: 14612 ± 3003 and 12280 ± 4632 photoreceptors/mm2 [95%CIs= -2413 to -702] p=0.0004, regularity: 88 ± 7% and 84 ± 12% [95%CIs= -4.67 to 0.04] p=0.054, dispersion: 19 ± 6% and 23 ± 10% [95%CIs= 0.5 to 4.24] p=0.013, spacing: 9 ± 1 microns and 10 ± 2microns [95%CIs= 0.40 to 1.27] p=0.0002; at 4° was: CD: 13377 ± 4339 and 12770 ± 4391 photoreceptors/mm2 [95%CIs= -1368 to 252] p=0.176, regularity:87 ± 9% and 86 ± 12% [95%CIs= -4.65 to 0.08] p=0.74, dispersion: 20 ± 8% and 20 ±9 % [95%CIs= -2.11 to 1.5] p=0.74, spacing:10 ± 2 microns and 10 ± 3 microns [95%CIs= -0.23 to 0.58] p=0.39. CONCLUSION: Adaptive optics imaging allows quantitative assessment of the photoreceptor mosaic pre- and post-PPV in patients with MH. There was a significant change to the photoreceptor mosaic related to the MH at 2° pre- and post-operatively. AO imaging enables high-resolution investigation of the photoreceptor remodeling process following surgery, which may allow for a more thorough assessment of surgical outcomes.

Argentinian flag sign during refractive laser-assisted cataract surgery - A case report.

Purpose: The Argentinian flag sign, or radial capsular tear extensions, is a rare complication when performing capsulorhexis during cataract surgery. Identifying and managing this complication early is important to prevent the tear from propagating around the periphery leading to posterior capsular rupture or vitreous loss. Observations: The Argentinian flag sign was previously reported in a case of femtosecond laser-assisted cataract surgery (FLACS). However, our report presents the first case after FLACS using the Catalys™ Precision Laser System, a platform which has been associated with a larger percentage of complete capsulotomies when compared to other platforms. Radial extensions of the capsular tear were observed in a 27-year-old male patient with an intumescent cataract in left eye. The complication was managed by manually redirecting and completing the radial extension flaps, along with delicate phacoemulsification and manual cutting of capsular edge in areas with significant capsular-IOL overlap. Conclusions and importance: Our case report highlights that despite the Catalys™ Precision Laser System success rates, radial tears may occur, especially in highly pressurized intumescent cataract. Therefore, surgeons must be prepared to optimize the surgical techniques to prevent the occurrence of this complication, as well as identify and manage it when it presents.

Incidence of giant cell arteritis mimicking non-arteritic anterior optic neuropathy.

PURPOSE: Giant cell arteritis (GCA) involving ophthalmic circulation often manifests as anterior ischemic optic neuropathy (AAION), presenting with severe vision loss and pallid optic disc edema. Non-arteritic anterior ischemic optic neuropathy (NAION) classically presents with segmental optic disc edema and corresponding altitudinal visual field defect (VFD) with small cup-to-disc ratio in the fellow eye. Differentiating these two entities is critical as GCA requires immediate treatment to prevent vision loss in the fellow eye. This study investigated how often GCA mimics NAION at presentation. METHODS: Retrospective chart review of patients with temporal artery biopsy (TAB) positive GCA with ocular manifestations seen at a tertiary neuro-ophthalmology practice between 2015 and 2020. Patients presenting with segmental non-pallid optic disc swelling and corresponding altitudinal VFD mimicking NAION were identified. RESULTS: The clinical presentation of 7.1% (3/42) of patients with TAB-positive GCA mimicked NAION. Two of three patients had cup-to-disc ratio of <0.3 in the fellow eye. Two patients were women, mean age was 67.3 ± 6.5 years, and mean presenting visual acuity was 0.45 ± 0.48 LogMAR. Two patients had a normal temporal artery ultrasound. Two of three patients had at least one systemic symptom of GCA at presentation and all had elevation of one or both inflammatory markers. CONCLUSIONS: There should be high index of suspicion for GCA, even in patients highly suspected to have NAION. Inflammatory markers must be checked in every patient with presumed NAION and TAB performed if one or both are elevated to avoid missing GCA.

Low probability of myasthenia Gravis in patients presenting to neuro-ophthalmology clinic for evaluation of isolated ptosis.

BACKGROUND: Concerning causes of ptosis, most notably third nerve palsy and Horner's syndrome, can be ruled out with normal ocular motility and pupillary examination. Myasthenia gravis (MG) however, rarely can present with ptosis as an isolated finding. We reviewed all patients presenting to tertiary neuro-ophthalmology practice with ptosis of unknown etiology to determine the frequency of MG. METHODS: Retrospective chart review of patients referred to a tertiary neuro-ophthalmology practice with undifferentiated ptosis. RESULTS: Sixty patients were included in the study. Twenty eight (47%) patients had ptosis along with various abnormalities of ocular motility and/or alignment and 32 (53%) had isolated unilateral ptosis defined as ptosis with absence of diplopia, or symptoms of generalized MG (GMG). Final diagnosis was aponeurotic ptosis due to levator palpebrae dehiscence in the majority (73%) of patients, while 10 (17%) were diagnosed with MG (6 with OMG, 4 with GMG). Diplopia was present in 9/10 patients with MG and 8/10 had abnormal ocular findings on clinical examination such as orbicularis oculi weakness, Cogan's lid twitch or fatiguability of ptosis on sustained upgaze. Only one patient referred for isolated unilateral ptosis was diagnosed with OMG and this patient had orbicularis oculi weakness. CONCLUSIONS: None of the patients with isolated unilateral ptosis and otherwise normal examination had MG. All patients eventually diagnosed with MG had diplopia or orbicularis weakness on examination. Thus, the yield of investigating patients with isolated ptosis for MG is exceedingly low.

Ischemic ocular manifestations of giant cell arteritis: A Canadian case series.

BACKGROUND: Diagnosing giant cell arteritis (GCA) can be challenging due to the variable clinical presentation and lack of systemic symptoms in approximately 20% of cases, which are termed occult GCA. GCA affects the ocular circulation in more than half of cases and can cause irreversible bilateral blindness if not rapidly recognized and treated. We compared clinical and laboratory findings of patients with occult and systemic temporal artery biopsy (TAB)-positive GCA with ocular manifestations. METHODS: Retrospective chart review of patients with TAB-positive GCA with ocular manifestations seen at a tertiary neuro-ophthalmology practice between 2015 and 2020. RESULTS: GCA was occult in 14.3% (6/42) and systemic in 85.7% (36/42) of patients. Occult GCA affected older patients (average age 84.6 ± 5.3 vs 75.9 ± 8.2). There was no significant difference in ESR or CRP levels between two cohorts. In patients with occult GCA, 83.3% (5/6) presented with AION, and 16.7% (1/6) with isolated cranial nerve six palsy (CN6P). In the systemic GCA cohort, 47.2% (17) presented with AION, 5.6% (2) with CRAO, 2.8% (1) with PION, 2.8% (1) with isolated CWS, 2.8% (1) had both CRAO and AION, 2.8% (1) isolated cranial nerve 4 palsy (CN4P), 2.8% (1) isolated CN6P, 22.2% (8) had history of amaurosis fugax but normal examination, and 11.1% (4) had visual symptoms but a normal exam. Three of the above patients with AION also had CN4P. Of patients diagnosed with AION, presenting visual acuity in the affected eye(s) was significantly worse in patients with occult GCA. Involvement of multiple ocular circulations was seen in six patients in the systemic group but none in the occult group. CONCLUSION: Occult GCA occurs more commonly in older patients who most of the time present with AION. Levels of inflammatory markers were similar in the occult and systemic groups. Though ocular ischemic manifestations were similar in both cohorts, in systemic GCA involvement of multiple ocular circulations is likely more common GCA should always be considered in older patients who present with signs of retinal and/or optic nerve head ischemia (AION and/or CWS) and new onset of CNPs, especially in patients where more than one ocular arterial circulation is involved.

Urgent Virtual Eye Assessments During the COVID-19 Pandemic.

Purpose: We aimed to evaluate the effectiveness and safety of a virtual eye assessment triage system implemented in response to COVID-19. Patients and Methods: We conducted a retrospective cross-sectional study using a consecutive sample of all virtual assessments conducted from March 24 to June 7, 2020 at a single ophthalmology center in Toronto, ON, Canada. Visual acuity and smartphone photographs were uploaded to an electronic assessment website. All patients were virtually triaged to an email or phone consult. Patient outcomes and satisfaction were assessed with a quality assurance survey. Primary outcome measures were the incidence of unplanned additional in-person visits and changes in treatment. Results: We performed 1535 virtual assessments. Of the triage pathways, 15% received an email consult only and 85% received a phone consult. Subsequently, 15% required an in-person assessment, 3% were referred elsewhere, and 0.1% were sent to the emergency. Presentations were most commonly cornea (52%) and retina (25%). They were non-urgent in 68% of cases and no pharmacologic treatment was required for 49%. Of 397 patients that responded out of 653 patients surveyed, 4% had an unplanned additional visit to the emergency, after which two patients underwent urgent retinal surgery and one patient underwent urgent glaucoma surgery. Two patients (0.5%) had a minor change in treatment. Conclusion: As routine regular in-person visits were not possible during the COVID-19 lockdown, virtual eye assessments provided an opportunity to triage patients. Virtual assessments have the potential to reduce in-person visits, but caution must be exercised to not miss vision-threatening conditions.

Ophthalmic findings in marginally housed women in a Canadian city.

OBJECTIVE: To assess the prevalence and common causes of ocular pathology experienced by vulnerable women with marginalized housing and/or a history of abuse, violence, and trafficking. METHODS: Using a stratified random sampling technique, we recruited 93 women living in 10 randomly selected women's shelters in Toronto, Canada between May and November of 2018. All English-speaking females older than the age of 18 were eligible to participate. Data on demographics, medical or ocular history, subjective visual acuity, and access to eye care were obtained. Comprehensive visual screening and dilated fundoscopy were performed for each participant. RESULTS: The median age was 40 years (interquartile range, 30.5-54 years) and the median duration of homelessness was 8 months (interquartile range, 2.25-20.5 months); 63.4% of participants reported a history of abuse, 44.9% experienced head trauma, 15.9% experienced eye trauma, 22.5% identified as refugees, and 2.17% (2 of 92) had been victims of human trafficking. The above variables were not significantly related to vision problem severity on univariate analysis. Based on the presenting visual acuity, 27.8% of participants (95% CI [18.9-38.2]) were found to have visual impairment. Visual impairment was mainly related to refractive error (54.8% [51 of 93]), however, nonrefractive pathology was also observed. Of all the participants, 64.5% had one or more abnormal findings during the vision screening, and 40.9% needed follow-up by an ophthalmologist. Most participants (96.7%) expressed interest in accessing free eye examinations. CONCLUSIONS: Visual impairment is highly prevalent among homeless women living in Toronto. Routine vision-screening programs present an opportunity to improve the ocular health of this vulnerable population.

Use of wearable point-of-view live streaming technology for virtual physical exam skills training.

We piloted a virtual teaching tool comprised of a chest-mounted smartphone streaming point-of-view footage over videoconferencing software to deliver a physical exam skills session. Compared to medical students taught via third person view through pre-recorded video followed by preceptor-led discussion, a higher proportion of students taught via point-of-view wearable technology reported improved knowledge of demonstrated skills and feeling engaged, comfortable interacting with their tutor, and better able to visualize demonstrated exam maneuvers. This accessible, affordable, and easily replicable innovation can potentially enhance virtual clinical skills teaching and enable novel distant clinical learning opportunities for healthcare professions students and educators.

Nous avons mis à l'essai un outil d'enseignement virtuel, notamment pour les cours de techniques d'examen physique, qui consiste dans le fait de porter un téléphone intelligent fixé sur la poitrine pour diffuser en direct, par le biais d'un logiciel de vidéoconférence, pour réaliser un examen physique plutôt que subjectif. Comparativement aux étudiants en médecine qui pour le cours ont visionné une vidéo préenregistrée prise par caméra objective, suivie d'une discussion dirigée par un précepteur, un plus grand nombre d'étudiants ayant suivi le cours par le biais d'une technologie portable avec par le biais d'un dispositif technologique portable déclarent avoir amélioré leurs connaissances sur les techniques présentées, se sentir engagés et à l'aise pour interagir avec l'enseignant, et avoir été en mesure de bien voir les gestes d'examen montrés. Cette innovation accessible, abordable et facilement reproductible pourrait permettre d'améliorer l'enseignement virtuel des habiletés cliniques et d'offrir de nouvelles possibilités d'enseignement.