PHOTORECEPTOR DAMAGE IN TERSON SYNDROME.

PURPOSE: To describe photoreceptor damage in patients with Terson syndrome as a potential cause for inconsistent clinical outcomes. METHODS: Clinical evaluation and retinal imaging in six patients. RESULTS: Four patients were women and two men, with an average age of 46.8 years (SD 8.9). Four patients suffered aneurysmal subarachnoid hemorrhage, one vertebral artery dissection, and one superior sagittal sinus thrombosis. In 11 eyes, a consistent pattern of outer retinal changes within the central retina affecting the ellipsoid zone and the outer nuclear layer was observed, indicating photoreceptor damage. Areas of photoreceptor damage showed poor spatial correlation with intraocular hemorrhage, particularly subinternal limiting membrane hemorrhage. The observed retinal abnormalities demonstrated incomplete recovery over long-term follow-up 3.5 to 8 years posthemorrhage, irrespective of surgical or conservative treatment strategy, and had variable impact on the patients' visual function. CONCLUSION: The observations suggest that photoreceptor damage in Terson syndrome likely represents a distinct manifestation of this condition, which could be caused by transient ischemia of the outer retina secondary to acute rise in intracranial pressure.

A Network Meta-Analysis of Retreatment Rates following Bevacizumab, Ranibizumab, Aflibercept, and Laser for Retinopathy of Prematurity.

TOPIC: To compare bevacizumab, ranibizumab, aflibercept, and laser treatment as primary therapies for retinopathy of prematurity (ROP) in terms of retreatment rate. CLINICAL RELEVANCE: Anti-VEGF agents are increasingly used as primary treatment for ROP and may provide superior outcomes compared with laser in posterior disease. Head-to-head comparisons between different anti-VEGFs are lacking. METHODS: We searched CENTRAL, Embase, MEDLINE, and CINAHL databases for randomized controlled trials and nonrandomized comparative studies that had been reported as of March 2022. We included studies that used bevacizumab, ranibizumab, aflibercept or laser for ROP with comparable cohorts and treatment criteria. Studies were evaluated by the Grading of Recommendations, Assessment, Development and Evaluation framework, and those with biased case selection, nonrandomized case-control, or lack of control group were excluded. Frequentist meta-analyses of proportions determined the absolute primary retreatment rate of each modality and Bayesian network meta-analyses compared pairs of treatments in type 1 and Zone I ROP. RESULTS: In all, 30 studies (4686 eyes) were included in the network meta-analyses. For type 1 ROP, single-treatment success rates (i.e., likelihood of needing no further treatment) were 89.3% (95% confidence interval [CI]: 83.8%-93.8%; n = 1552) for laser, 87.0% (95% CI: 78.6%-93.8%; n = 2081) for bevacizumab, 80.7% (95% CI: 62.0%-94.4%; n = 326) for aflibercept, and 74.0% (95% CI: 62.7%-84.1%; n = 727) for ranibizumab. Bayesian network meta-analysis indicates that laser treatment is associated with a significant 62% (95% credible interval [CrI]: 16%-83%) reduction in retreatment risk compared with ranibizumab, while no significant difference was found among other pairwise comparisons. The mean ± standard error of the mean times to secondary treatment following primary aflibercept (12.96 ± 0.47 weeks) and bevacizumab (11.36 ± 0.54 weeks) therapy were significantly longer than that for primary ranibizumab (9.29 ± 0.43weeks) therapy (P = 7 × 10-7 and P = 9 × 10-3, respectively). For Zone I ROP, single-treatment success rates were 91.2% (95% CI: 83.6-96.9; n = 231) for bevacizumab, 78.3% (95% CI: 61.4-91.9; n = 100) for ranibizumab, and 65.9% (95% CI: 41.4-87.2; n = 158) for laser treatment. In this case, Bayesian network meta-analysis suggests that primary bevacizumab is associated with a significant 67% (95% CrI:10%-90%) reduction in retreatment risk compared with laser treatment. CONCLUSIONS: Laser was associated with a lower rate of retreatment than ranibizumab in type 1 ROP (Zones I and II combined), while bevacizumab was associated with a lower rate of retreatment than laser in Zone I ROP. Aflibercept and bevacizumab demonstrate longer duration of action than ranibizumab for ROP.

Multimodal Evaluation and Management of Wagner Syndrome-Three Patients from an Affected Family.

Wagner syndrome is a rare autosomal dominant vitreoretinopathy caused by mutations in chondroitin sulphate proteoglycan 2 (CSPG2)/Versican (VCAN). Here, we present a retrospective case series of a family pedigree with genetically confirmed Wagner syndrome (heterozygous VCAN exon 8 deletion), as follows: a 34-year-old mother (P1), 12-year-old daughter (P2), and a 2-year-old son (P3). The phenotype included early-onset cataract (P1), optically empty vitreous with avascular membranes (P1, 2), nasal dragging of optic nerve heads associated with foveal hypoplasia (P1, 2), tractional retinoschisis on optical coherence tomography (P2), and peripheral circumferential vitreo-retinal interface abnormality resembling white-without-pressure (P3) progressing to pigmented chorio-retinal atrophy (P1, 2). P2 developed a macula-off retinal detachment, which was treated initially with encircling band + vitrectomy + gas, followed by vitrectomy + heavy silicone oil tamponade for re-detachment from new inferior breaks. Strong vitreo-retinal adhesion was noted intraoperatively, which prevented the separation of posterior hyaloid beyond the equator. Electroretinograms from P1&2 demonstrated attenuated b-waves, a-waves, and flicker responses in light- and dark-adapted conditions, suggestive of generalised retinal dysfunction. Our patients demonstrated the clinical spectrum of Wagner syndrome, highlighting nasal dragging with foveal disruption as a distinguishing feature from other inherited vitreoretinopathies. Surgical outcomes demonstrate significant challenges in managing vitreo-retinal traction and need for further research into strategies to prevent sight loss.

A Carrier Female Manifesting an Unusual X-Linked Retinoschisis Phenotype Associated with the Pathogenic Variant c.266delA, p.(Tyr89LeufsTer37) in RS1, and Skewed X-Inactivation.

X-linked retinoschisis (XLRS) is the most common juvenile macular degeneration in males. Unlike most other X-linked retinal dystrophies, carrier heterozygous females are very rarely reported to show clinical features of the disease. Herein, we describe unusual retinal features in a 2-year-old female infant with family history and genetic testing consistent with XLRS.

Morphological and functional parameters in X-linked retinoschisis patients-A multicentre retrospective cohort study.

Introduction: X-linked retinoschisis (XLRS) is a potential target for gene supplementation approaches. To establish potential structural and functional endpoints for clinical trials, a comprehensive understanding of the inter-eye symmetry, relationship between structural and functional parameters, and disease progression is vital. Methods: In this retrospective multicentre study, 118 eyes of 59 XLRS patients with RS1 mutations were assessed. Information from center databases included: RS1 variant; age at presentation; best-corrected visual acuity (BCVA), central retinal thickness (CRT), macular volume (MV) at presentation and at the last follow up; full-field electroretinogram (ERG) findings; presence of peripheral retinoschisis and complications (vitreous hemorrhage, retinal detachment); treatment with systemic or topical carbonic anhydrase inhibitors (CAI). Results: Inter-eye symmetry revealed strong correlation in CRT (r = 0.77; p < 0.0001) and moderate correlations in MV (r = 0.51, p < 0.0001) and BCVA (r = 0.49; p < 0.0001). Weak or no correlations were observed between BCVA and structural parameters (CRT, MV). Peripheral retinoschisis was observed in 40 (68%), retinal detachment in 9 (15%), and vitreous hemorrhage in 5 (8%) patients, respectively. Longitudinal examinations (mean, 4.3 years) showed no BCVA changes; however, a reduction of the CRT (p = 0.02), and MV (p = 0.01) was observed. Oral and/or topical CAI treatment did not significantly alter the CRT (p = 0.34). Discussion: The XLRS phenotype demonstrates a strong CRT symmetry between the eyes within individual patients and stable BCVA over several years. BCVA exhibits a weak correlation with the morphological parameters of retinal thickness (CRT MV). In our cohort, longitudinal functional changes were not significant, likely attributed to the short average follow-up period. Furthermore, CAI treatment didn't influence both morphological and functional outcomes.

Flying baby optical coherence tomography alters the staging and management of advanced retinopathy of prematurity.

PURPOSE: To report the use of flying baby spectral domain optical coherence tomography (SD-OCT) on infants with advanced retinopathy of prematurity (ROP), where clinical findings alone failed to differentiate between retinoschisis and retinal detachment. METHODS: Prospective, non-interventional case-series study of three premature infants with advanced ROP of clinically uncertain stage, after examination by indirect ophthalmoscopy. To confirm the diagnosis, table-mounted SD-OCT retinal imaging was performed with the infant held in the flying baby position under topical ocular anaesthesia only. Spectral domain optical coherence tomography (SD-OCT) findings were correlated with clinical examination and ultra-widefield scanning laser ophthalmoscopy to determine disease stage and appropriate management. RESULTS: The flying baby position was well tolerated, and SD-OCT images of central and peripheral retina were successfully obtained in all three cases. Additional information provided by the SD-OCT changed the ROP staging from 3 to 4 in one case, which subsequently required surgical treatment. In two other cases, clinical suspicion of stage 4 ROP was overruled as SD-OCT revealed tractional retinoschisis rather than full-thickness retinal detachment, thereby avoiding the need for immediate surgical intervention. CONCLUSIONS: In this case-series study, flying baby SD-OCT provided a rapid and widely accessible imaging approach that overruled clinical findings and altered classification and management of infants with advanced ROP. The methodology was suitable for outpatient settings with no risks associated with systemic anaesthesia. The increased use of OCT imaging will make apparent how structural information is useful in management of ROP and may influence future classification of the disease.

Retinal imaging in infants.

Digital retinal imaging is at the core of a revolution that is continually improving the screening, diagnosis, documentation, monitoring, and treatment of infant retinal diseases. Historically, imaging the retina of infants had been limited and difficult to obtain. Recent advances in photographic instrumentation have significantly improved the ability to obtain high quality multimodal images of the infant retina. These include color fundus photography with different camera angles, ultrasonography, fundus fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography. We provide a summary of the current literature on retinal imaging in infants and highlight areas where further research is required.

Improved Diagnosis of Retinal Laser Injuries Using Near-Infrared Autofluorescence.

PURPOSE: To assess whether near infrared autofluorescence (NIR-AF) imaging is a useful imaging modality in the diagnosis of handheld laser retinal injuries. DESIGN: Retrospective observational case series. METHODS: Twelve patients identified to have handheld laser retinal injuries were included at 2 academic centers. Patients underwent ophthalmic assessment and retinal imaging including fundus photography, optical coherence tomography (OCT), conventional blue autofluorescence (B-AF), and NIR-AF imaging. RESULTS: In all cases, lesions consistent with retinal laser injury were detected by NIR-AF imaging. The lesions showed a characteristic appearance with central hyperfluorescence and surrounding hypofluorescence, although the number and extent of lesions varied between patients. Findings using other imaging modalities were variable: on color fundus photography these included localized pigmentary changes and on OCT imaging an ellipsoid zone interruption or outer nuclear layer changes. Only subtle changes were evident on B-AF imaging. Other macular conditions, such as poppers retinopathy or solar maculopathy, which may have similar findings on OCT imaging as laser damage, can be differentiated using NIR-AF imaging. CONCLUSION: An increased incidence of retinal injuries secondary to handheld lasers has been reported in recent years. We show that the diagnosis and full extent of retinal laser injuries is best demonstrated by NIR-AF, as other modalities give variable results. We propose that NIR-AF should be included when investigating patients suspected of macular injury secondary to exposure to handheld lasers.

Modernising ophthalmology teaching: introducing a live and interactive video link.

The Health Education Thames Valley (HETV) Ophthalmology training programme holds compulsory weekly afternoon teaching sessions in Oxford. Traditionally, trainees travelled considerable distances to attend this teaching. Commuting is a known stress factor and car use has environmental, monetary and health costs. To reduce trainee costs, travelling time and improve teaching experience, we introduced an interactive and live video link across HETV. Teaching sessions were broadcast live using free videolink software between 3 sites. New hardware cost £200 per site. Attendees completed weekly feedback questionnaires on the videolink over 9 months. Over this period, the deanery had 22 trainees with 12 working outside Oxford. Projected annual travel savings were calculated. On average 10.8 trainees (49.1%) completed weekly questionnaires: 5.1 (range:3-8) were trainees working outside Oxford and 5.6 trainees (range 3-10) working in Oxford. Attendee responses showed on average: 78.6% learnt as much as attending in person; 91.17% felt interaction through the videolink was adequate; and 94.6% remained keen on telecommuting. Of the trainees in Oxford, 26.5% felt that the videolink interfered with the teaching session. The average videolink quality rating was 3.73 (1:poor; 5:excellent). Annually, the videolink will save each trainee working outside Oxford an average of 2120 kilometres in travel and £594 in expenses. Most attendees felt the videolink was a valuable tool in delivering teaching sessions. It eliminates unnecessary journeys and travel related stress. Within HETV, a £600 initial investment for new hardware would save trainees approximately £7128 annually. There is potential in expanding the role of the videolink to allow guest speakers worldwide to easily contribute to teaching sessions, eliminating unnecessary travel. This model could be adapted to postgraduate training programmes nationally to improve trainee wellbeing by reducing travelling time and costs.

Early term effects of rhBMP-2 on pedicle screw fixation in a sheep model: histomorphometric and biomechanical analyses.

BACKGROUND: The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on pedicle screw pullout force and its potential to improve spinal fixation have not previously been investigated. rhBMP-2 on an absorbable collagen sponge (ACS) carrier was delivered in and around cannulated and fenestrated pedicle screws in a sheep lumbar spine instability model. Two control groups (empty screw and ACS with buffer) were also evaluated. We hypothesized that rhBMP-2 could stimulate bone growth in and around the cannulated and fenestrated pedicle screws to improve early bone purchase. METHODS: Eight skeletally mature sheep underwent destabilizing laminectomies at L2-L3 and L4-L5 followed by stabilization with pedicle screw and rod constructs. An ACS carrier was used to deliver 0.15 mg of rhBMP-2 within and around the cannulated and fenestrated titanium pedicle screws. Biomechanics and histomorphometry were used to evaluate the early term results at 6 and 12 postoperative weeks. RESULTS: rhBMP-2 was unable to improve bony purchase of the cannulated and fenestrated pedicle screws compared to both control groups. Although rhBMP-2 groups had pullout forces that were less than both control groups, both rhBMP-2 groups had pullout force values exceeding 2,000 N, which was comparable to previously published results for unmodified pedicle screws. Significant differences in the percentages of bone in peri-screw tissues was not observed amongst the four treatment groups. Microradiography and quantitative histomorphometry showed that at 6 weeks, rhBMP-2 induced peri-screw remodeling regions containing peri-implant bone which was hypodense with respect to surrounding native trabeculae. A moderate correlation between biomechanical pullout variables and histomorphometry data was observed. CONCLUSIONS: The design of the cannulated and fenestrated pedicle screw was able to facilitate new bone formation to achieve high pullout forces. However, delivery of rhBMP-2 should be carefully controlled to prevent excessive bone remodeling which could cause early screw loosening.

Integrating retinal simulation with a peer-assessed group OSCE format to teach direct ophthalmoscopy.

OBJECTIVE: To describe the conception and evaluation of a novel educational intervention to teach direct ophthalmoscopy with retinal simulators using a peer-assessed group objective structured clinical examination (OSCE) format. DESIGN: Prospective, single-centre educational trial at Oxford University Medical School, Oxford, U.K. PARTICIPANTS: A total of 160 consecutive undergraduate fifth-year medical students participated in the study. METHODS: Students identified prior experience, teaching, examination, and feedback relevant to direct ophthalmoscopy. Students self-evaluated their perceived confidence across 6 domains of direct ophthalmoscopy examination before and after the educational intervention using a Likert-type psychometric scale. Wilcoxon matched pair testing was used to determine statistical significance for each domain. RESULTS: The group OSCE intervention increased confidence in direct ophthalmoscopy overall from 2.5% to 63.8% (p < 0.001). Confidence improved in all 6 domains, most significantly in controls of ophthalmoscope (p < 0.001) and sequence of examination (p < 0.001) but also in the identification and interpretation of retinal signs (p < 0.001). Students rated the tutorial as very effective or effective across all 6 domains, and 96.29% rated the tutorial as effective overall. CONCLUSIONS: Retinal simulation, integrated with a peer-assessed group OSCE format, is effective in increasing confidence in all aspects of direct ophthalmoscopy. It may be insufficient alone for training in the identification and interpretation of posterior segment clinical signs. Diminishing ophthalmology clerkships worldwide require ophthalmologists to identify innovative teaching methods, using modern technology and pedagogy to deliver high-quality, yet high-throughput, training in direct ophthalmoscopy. This novel teaching strategy may be considered by ophthalmologists responsible for direct ophthalmoscopy training in a teaching hospital context.

Incidence, mechanism and outcomes of schisis retinal detachments revealed through a prospective population-based study.

AIM: To determine the incidence, presentation and outcomes of progressive sight-threatening retinal detachment (RD) complicating degenerative retinoschisis. METHODS: We conducted the first prospective population-based epidemiological study of progressive schisis detachment over a 1-year period (2014-2015) in the UK. Case ascertainment was via monthly British Ophthalmological Surveillance Unit reporting cards sent to all ophthalmologists in the UK. For each reported case, data were collected using incident and 6 months follow-up questionnaires gathering information including demographic, presenting symptoms, retinal findings, primary management, primary outcome, secondary management and secondary outcome. RESULTS: Fifty-five cases of progressive schisis RD were identified with similar age distribution to conventional rhegmatogenous RD (mean age 64.0 years, range 20-88), and male-to-female ratio of 2.3:1. The locations of schisis detachments were predominantly supratemporal (46.7%) and infratemporal (35.6%). At least 70% of schisis RD were associated with posterior vitreous detachment (PVD) at presentation and 21% with grade B-C proliferative vitreoretinopathy. Primary management consisted of pars plana vitrectomy (82%), scleral buckle (9%), observation (4%), laser (2%) and combined vitrectomy-buckle (2%). Primary reattachment rate was 70%. Final reattachment rate was 87% with mean best-corrected visual acuity of 0.49 Decimal (SD 0.34) for fovea-on and 0.42 Decimal (SD 0.29) for fovea-off schisis detachments at mean follow-up of 8.7 months (SE 1.0). CONCLUSIONS: The estimated annual incidence of progressive schisis RD was 0.85 per million population (95% CI 0.64 to 1.11), equivalent to around 0.66% of all rhegmatogenous RD. PVD may play a key pathogenic role in the development of progressive schisis detachments. Surgical outcomes are inferior to those of conventional rhegmatogenous RD.

Effect of lens epithelial cell aspiration on postoperative capsulorhexis contraction with the use of the AcrySof intraocular lens: randomized clinical trial.

PURPOSE: To determine whether aspiration of lens epithelial cells (LECs) from under the anterior capsule reduces postoperative contraction of the capsulorhexis aperture. SETTING: Stoke Mandeville Hospital, Aylesbury, Buckinghamshire, United Kingdom. METHODS: This prospective randomized observer-masked study comprised 100 patients who had routine phacoemulsification by the same surgeon at a district general hospital in the United Kingdom. The postoperative changes in capsulorhexis apertures and anterior capsule opacification (ACO) between Group A (aspiration of LECs) and Group B (control) were compared. Digital retroillumination images of the capsulorhexis aperture were taken 1 week and 3 months postoperatively. The area of capsulorhexis aperture was determined with computer software, and capsule opacification was graded subjectively. RESULTS: Three months postoperatively, the mean decrease in capsulorhexis aperture was 1.9% in Group A and 5.6% in Group B (P = .02). The ACO at 3 months was grade 2 in 44% of eyes in Group A and in 61% in Group B (P = .13). CONCLUSION: Aspiration of LECs from the anterior capsule was a safe procedure that reduced capsulorhexis aperture contraction 3 months after cataract surgery.

The Influence of Exercise on Perceived Pain and Disability in Patients With Lumbar Spinal Stenosis: A Systematic Review of Randomized Controlled Trials.

Lumbar spinal stenosis (LSS) is an increasingly prevalent condition that has major health and economic implications. While there are many options for the treatment of LSS, exercise is widely considered a first-line intervention as it is associated with reduced complications and cost as compared to more invasive options. Currently, it is not clear if exercise is an effective approach to managing pain and perceived disability in patients with symptomatic LSS. Therefore, the purpose of this systematic review is to evaluate the published literature that has investigated exercise as a primary intervention for LSS. A search was conducted in electronic databases including PubMed, PEDro, SPORTDiscus, CINAHL, and AMED using the key words lumbar spinal stenosis, exercise, physical therapy, rehabilitation, and conservative treatment. Inclusion criteria consisted of published randomized controlled trials written in English that included exercise as the primary treatment in at least one of the groups, and had reported measures of pain and disability clearly stated. The search identified 310 studies of which 5 met all the inclusion parameters. Exercise appears to be an efficacious intervention for pain, disability, analgesic intake, depression, anger, and mood disturbance among patients with LSS. Further research is needed to determine which type of exercise is the most effective in managing symptoms associated with lumbar spinal stenosis.

Ultra-widefield retinal imaging through a black intraocular lens.

PURPOSE: To evaluate the feasibility of ultra-widefield retinal imaging in patients with near infrared (IR)-transmitting black intraocular lenses (IOLs). SETTING: Oxford Eye Hospital, Oxford, United Kingdom. DESIGN: Laboratory evaluation of a diagnostic technology with interventional case report. METHODS: The field of retinal imaging through a Morcher poly(methyl methacrylate) (PMMA) black IOL was determined in a purpose-built adult schematic model eye with the HRA2 Spectralis confocal scanning laser ophthalmoscope using standard imaging, Staurenghi retina lens-assisted imaging, and ultra-widefield noncontact imaging. Retinal imaging using each modality was then performed on a patient implanted with another Morcher PMMA black IOL model. RESULTS: Ultra-widefield noncontact imaging and lens-assisted imaging captured up to 150 degrees of field (versus 40 degrees with a standard confocal scanning laser ophthalmoscope). Ultra-widefield retinal images were successfully acquired in a patient eye with a black IOL. CONCLUSIONS: This study has identified the first ultra-widefield retinal imaging modalities for patients with near IR-transmitting black IOLs. Should larger studies confirm this finding, noncontact ultra-widefield confocal scanning laser ophthalmoscopy might be considered the gold standard imaging technique for retinal surveillance in patients with near IR-transmitting black IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.