Early vitrectomy for exogenous endophthalmitis following surgery.

BACKGROUND: Endophthalmitis is a sight-threatening emergency that requires prompt diagnosis and treatment. The condition is characterised by purulent inflammation of the intraocular fluids caused by an infective agent. In exogenous endophthalmitis, the infective agent is foreign and typically introduced into the eye through intraocular surgery or open globe trauma. OBJECTIVES: To assess the potential role of combined pars plana vitrectomy and intravitreal antibiotics in the acute management of exogenous endophthalmitis, versus the standard of care, defined as vitreous tap and intravitreal antibiotics. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5); Ovid MEDLINE; Ovid Embase; the International Standard Randomised Controlled Trial Number registry; ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. There were no restrictions to language or year of publication. The date of the search was 5 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared pars plana vitrectomy and intravitreal injection of antibiotics versus intravitreal injection of antibiotics alone, for the immediate management of exogenous endophthalmitis. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two review authors independently screened search results and extracted data. We considered the following outcomes: visual acuity improvement and change in visual acuity at three and six months; additional surgical procedures, including vitrectomy and cataract surgery, at any time during follow-up; quality of life and adverse effects. We assessed the certainty of the evidence using the GRADE approach.  MAIN RESULTS: We identified a single RCT that met our inclusion criteria. The included RCT enrolled a total of 420 participants with clinical evidence of endophthalmitis, within six weeks of cataract surgery or secondary intraocular lens implantation. Participants were randomly assigned according to a 2 x 2 factorial design to either treatment with vitrectomy (VIT) or vitreous tap biopsy (TAP) and to treatment with or without systemic antibiotics. Twenty-four participants did not have a final follow-up: 12 died, five withdrew consent to be followed up, and seven were not willing to return for the visit.  The study did not report visual acuity according to the review's predefined outcomes. At three months, 41% of all participants achieved 20/40 or better visual acuity and 69% had 20/100 or better acuity. The study authors reported that there was no statistically significant difference in visual acuity between treatment groups (very low-certainty evidence). There was low-certainty evidence of a similar requirement for additional surgical procedures (risk ratio RR 0.90, 95% confidence interval 0.66 to 1.21). Adverse effects included: VIT group: dislocated intraocular lens (n = 2), macular infarction (n = 1). TAP group: expulsive haemorrhage (n = 1). Quality of life and mean change in visual acuity were not reported.  AUTHORS' CONCLUSIONS: We identified a single RCT (published 27 years ago) for the role of early vitrectomy in exogenous endophthalmitis, which suggests that there may be no difference between groups (VIT vs TAP) for visual acuity at three or nine months' follow-up.   We are of the opinion that there is a clear need for more randomised studies comparing the role of primary vitrectomy in exogenous endophthalmitis. Moreover, since the original RCT study, there have been incremental changes in the surgical techniques with which vitrectomy is performed. Such advances are likely to influence the outcome of early vitrectomy in exogenous endophthalmitis.

Patient generated aerosol in the context of ophthalmic surgery.

OBJECTIVE: To assess the patterns of patient generated aerosol in the context of ophthalmic surgery and ophthalmic examinations. To inform medical teams regarding potential hazards and suggest mitigating measures. METHODS: Qualitatively, real-time time videography assessed exhalation patterns from simulated patients under different clinical scenarios using propylene glycol from an e-cigarette. Quantitatively, high-speed Schlieren imaging was performed to enable high resolution recordings analysable by MATLAB technical computing software. RESULTS: Without a face mask, the standard prior to COVID 19, vapour was observed exiting through the opening in the drape over the surgical field. The amount of vapour increased when a surgical mask was worn. With a taped face mask, the amount of vapour decreased and with inclusion of a continuous suction device, the least amount of vapour was seen. These results were equivocal when the patient was supine or sitting upright. High-speed Schlieren imaging corroborated these findings and in addition showed substantial increase in airflow egress during coughing and with ill-fitting face masks. CONCLUSION: Advising patients to wear a surgical mask at the time of ophthalmic interventions potentially contaminants the ocular field with patient generated aerosol risking endophthalmitis. Surgeon safety can be maintained with personal protective equipment to mitigate the increased egress of vapour from the surgical drape and taping, with or without suction is advisable, whilst meticulous hygiene around lenses is required at the time of slit lamp examination.

Transplantation of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells in Macular Degeneration.

PURPOSE: Transplantation of human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells offers the potential for benefit in macular degeneration. Previous trials have reported improved visual acuity (VA), but lacked detailed analysis of retinal structure and function in the treated area. DESIGN: Phase 1/2 open-label dose-escalation trial to evaluate safety and potential efficacy (clinicaltrials.gov identifier, NCT01469832). PARTICIPANTS: Twelve participants with advanced Stargardt disease (STGD1), the most common cause of macular degeneration in children and young adults. METHODS: Subretinal transplantation of up to 200 000 hESC-derived RPE cells with systemic immunosuppressive therapy for 13 weeks. MAIN OUTCOME MEASURES: The primary end points were the safety and tolerability of hESC-derived RPE cell administration. We also investigated evidence of the survival of transplanted cells and measured retinal structure and function using microperimetry and spectral-domain OCT. RESULTS: Focal areas of subretinal hyperpigmentation developed in all participants in a dose-dependent manner in the recipient retina and persisted after withdrawal of systemic immunosuppression. We found no evidence of uncontrolled proliferation or inflammatory responses. Borderline improvements in best-corrected VA in 4 participants either were unsustained or were matched by a similar improvement in the untreated contralateral eye. Microperimetry demonstrated no evidence of benefit at 12 months in the 12 participants. In one instance at the highest dose, localized retinal thinning and reduced sensitivity in the area of hyperpigmentation suggested the potential for harm. Participant-reported quality of life using the 25-item National Eye Institute Visual Function Questionnaire indicated no significant change. CONCLUSIONS: Subretinal hyperpigmentation is consistent with the survival of viable transplanted hESC-derived RPE cells, but may reflect released pigment in their absence. The findings demonstrate the value of detailed analysis of spatial correlation of retinal structure and function in determining with appropriate sensitivity the impact of cell transplantation and suggest that intervention in early stage of disease should be approached with caution. Given the slow rate of progressive degeneration at this advanced stage of disease, any protection against further deterioration may be evident only after a more extended period of observation.

Assessment of AAV Vector Tropisms for Mouse and Human Pluripotent Stem Cell-Derived RPE and Photoreceptor Cells.

Adeno-associated viral vectors are showing great promise as gene therapy vectors for a wide range of retinal disorders. To date, evaluation of therapeutic approaches has depended almost exclusively on the use of animal models. With recent advances in human stem cell technology, stem cell-derived retina now offers the possibility to assess efficacy in human organoids in vitro. Here we test six adeno-associated virus (AAV) serotypes [AAV2/2, AAV2/9, AAV2/8, AAV2/8T(Y733F), AAV2/5, and ShH10] to determine their efficiency in transducing mouse and human pluripotent stem cell-derived retinal pigment epithelium (RPE) and photoreceptor cells in vitro. All the serotypes tested were capable of transducing RPE and photoreceptor cells in vitro. AAV ShH10 and AAV2/5 are the most efficient vectors at transducing both mouse and human RPE, while AAV2/8 and ShH10 achieved similarly robust transduction of human embryonic stem cell-derived cone photoreceptors. Furthermore, we show that human embryonic stem cell-derived photoreceptors can be used to establish promoter specificity in human cells in vitro. The results of this study will aid capsid selection and vector design for preclinical evaluation of gene therapy approaches, such as gene editing, that require the use of human cells and tissues.

The Effect of Multispot Laser Panretinal Photocoagulation on Retinal Sensitivity and Driving Eligibility in Patients With Diabetic Retinopathy.

IMPORTANCE: Panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR) may lead to peripheral field loss that prevents driving. Anti-vascular endothelial growth factor agents are proposed as treatments for PDR that spare peripheral vision. If multispot lasers cause less visual field loss, continuing to perform PRP may be justified. OBJECTIVE: To assess the effect of bilateral multispot laser PRP on retinal sensitivity and driving visual fields in PDR. DESIGN, SETTING, AND PARTICIPANTS: This prospective nonrandomized interventional cohort analysis performed at a tertiary referral center included 43 laser-naive patients with PDR that required bilateral PRP. Participants were recruited from June 27, 2012, to October 14, 2013. At baseline and 6-month follow-up, patients underwent detailed static and kinetic perimetry, microperimetry, optical coherence tomography, wide-field color fundus photography, and fluorescein angiography. Quantitative change in retinal sensitivity was assessed by comparing the mean global retinal sensitivity before and after laser treatment and by comparing the modeled hill of vision by deriving a volumetric measure. Final follow-up was completed on May 21, 2014. INTERVENTIONS: Multispot laser treatment was applied using standard parameters, until neovascularization regressed or complete retinal coverage was achieved. MAIN OUTCOMES AND MEASURES: Participants who passed the Esterman binocular visual field test for driving in the United Kingdom (at least 120° horizontal field with no significant defects within the central 20°) and full-field and macular retinal sensitivity. RESULTS: Of the 43 patients (17 men; 26 women; mean [SD] age, 46.6 [13.3] years), 38 (88%) completed the study. Before treatment, 41 of 43 patients (95%) passed the Esterman visual field test for driving; after completion of laser treatment, 35 of 38 patients (92%) passed. The mean (SD) change in retinal sensitivity on static perimetry was -1.4 (3.7) (95% CI, -2.7 to -0.1) dB OD and -2.4 (2.9) (95% CI, -3.4 to -1.4) dB OS. Mean (SD) 4° macular sensitivity decreased by 3.0 (5.2) dB OD and 2.6 (5.4) dB OS. CONCLUSIONS AND RELEVANCE: This prospective study investigating the effects of multispot laser PRP on retinal sensitivity demonstrates a high likelihood of retaining eligibility to drive based on adequate visual field. A mild loss of retinal sensitivity was detected at 6 months after completion of laser treatment. Further change to visual fields may have occurred with longer follow-up. This study provides information that might be used to counsel patients requiring PRP and informs the debate regarding the role of anti-vascular endothelial growth factor therapy in patients with PDR who might otherwise receive laser treatment.

Long-term effect of gene therapy on Leber's congenital amaurosis.

BACKGROUND: Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS: We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS: Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS: Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

Blepharoptosis following anterior segment surgery: a new theory for an old problem.

Blepharoptosis is a well-known complication following anterior segment surgery. However, its precise aetiology remains elusive. There are currently two widely held views on the pathogenesis of persistent postoperative ptosis, namely the speculum and bridle suture theories. However, both suggested explanations fail to address important anatomical and epidemiological features of this condition. Until now, the majority of published literature describing persistent postoperative ptosis following anterior segment surgery has largely concentrated on dehiscence of the levator aponeurosis as the common mechanism underlying this postoperative complication. However, numerous studies have failed to show any correlation between pre or postoperative skin crease positions in such patients. This review article discusses previously proposed mechanisms responsible for both transient and persistent ptosis. Furthermore, we propose an alternative mechanism for the development of ptosis following anterior segment surgery, namely horizontal stretch of the upper eyelid induced by the use of the speculum. This mechanism also provides a plausible explanation for less commonly described oculoplastic complications, such as lower lid malpositions, following anterior segment surgery. Postoperative ptosis may also act as a paradigm for the development of involutional ptosis in general. In view of the frequency with which ophthalmologists perform anterior segment procedures such as cataract surgery, postoperative ptosis represents a significant concern for all ocular surgeons. Identifying the underlying mechanism is imperative, not only to identify those patients at greatest risk, but also to perhaps provide novel surgical approaches to the management of this complication.

A newborn with ankyloblepharon filiforme adnatum: a case report.

Ankyloblepharon filiforme adnatum is a rare congenital anomaly. We report a case of ankyloblepharon filiforme adnatum in a newborn Caucasian male whose paediatric examination was otherwise unremarkable. Ankyloblepharon filiforme adnatum can present as an isolated finding, in association with other anomalies, or as part of a well-defined syndrome.