Photobiomodulation for non-exudative age-related macular degeneration

BACKGROUND: Age‐related macular degeneration (AMD) is one of the leading causes of blindness in high‐income countries. The majority of cases of AMD are of the non‐exudative type. Experts have proposed photobiomodulation (PBM) therapy as a non‐invasive procedure to restore mitochondrial function, upregulate cytoprotective factors and prevent apoptotic cell death in retinal tissue affected by AMD. OBJECTIVES: To assess the effectiveness and safety of PBM compared to standard care, no treatment or sham treatment for people with non‐exudative AMD. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (Issue 5, 2020), Ovid MEDLINE, Embase, ISRCTN, ClinicalTrials.gov and the WHO ICTRP to 11 May 2020 with no language restrictions. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) on participants receiving any type of PBM therapy for non‐exudative AMD compared to standard care, sham treatment or no treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We considered the following outcome measures at 12 months: best‐corrected visual acuity (BCVA) ; contrast sensitivity; near vision; low luminance density score; reading speed; vision‐related quality of life score; and adverse events such as progression of AMD and conversion to exudative AMD. We graded the certainty of the evidence using GRADE. MAIN RESULTS: We included two published RCTs from single centres in the UK and Canada, which recruited 60 participants (60 eyes) and 30 participants (46 eyes) respectively. Participants in these trials were people with non‐exudative AMD with Age‐Related Eye Disease Study (AREDS) categories 2 to 4. One study compared single wavelength PBM with no treatment. This study was at risk of performance bias because the study was not masked, and there was attrition bias. One study compared multi‐wavelength PBM with sham treatment and conflicts of interest were reported by study investigators. We also identified three eligible ongoing RCTs from searching the clinical trials database. When comparing PBM with sham treatment or no treatment for non‐exudative AMD, there was no evidence of any meaningful clinical difference in BCVA at 12 months (mean difference (MD) 0.02 logMAR, 95% confidence interval (CI) ‐0.02 to 0.05; 2 RCTs, 90 eyes; low‐certainty evidence). One study comparing multi‐wavelength PBM with sham treatment showed an improvement in contrast sensitivity at Level E (18 cycles/degree) at 12 months (MD 0.29 LogCS, 95% CI 0.23 to 0.35; 1 RCT, 46 eyes; low‐certainty evidence). Visual function and health‐related quality of life scores were comparable between single wavelength PBM and no treatment groups at 12 months (VFQ‐48 score MD 0.43, 95% CI ‐0.17 to 1.03; P = 0.16; 1 RCT, 47 eyes; low‐certainty evidence). When comparing PBM with sham treatment or no treatment for non‐exudative AMD, there was no evidence of any meaningful clinical difference in conversion to exudative AMD (risk ratio (RR) 0.97, 95% CI 0.17 to 5.44; 2 RCTs, 96 eyes; very low‐certainty evidence) at 12 months. There was inconclusive evidence that single wavelength PBM prevents the progression of AMD (RR 0.79, 95% CI 0.41 to 1.53; P = 0.48; 1 RCT, 50 eyes; low‐certainty evidence). Disease progression was defined as the development of advanced AMD or significant increase in drusen volume. No included study reported near vision, low luminance vision or reading speed outcomes

Development of virtual ophthalmic surgical skills training

Background: This study aims to assess whether ophthalmic surgical skills can be taught successfully online to a diverse international and interprofessional student group. Methods: Mixed methods study involving 20 students and 5 instructors. Each student completed a pre-session and post-session questionnaire to assess their perceptions regarding online instruction. Changes in questionnaire responses were analysed using Wilcoxon signed rank (SPSS 25). Semi-structured interviews were conducted to assess instructor perceptions towards virtual surgical skills teaching. Thematic analysis was undertaken using NVivo 12.0 software. Results: There was a 100% completion rate of pre- and post-session questionnaires. Prior to the session, lack of instructor supervision and inability to provide constructive feedback were emergent themes from students. Pre-session concerns regarding online delivery: 40% of students thought their view of skills demonstration would be negatively impacted, 60% their level of supervision and 55% their interaction with instructors. Following the session 10%, 15% and 5% held this view respectively. All students were ‘satisfied’ or ‘very satisfied’ regarding the ‘Surgeon’s View’ camera angle as well as the use of breakout rooms. 75% perceived an improvement in their confidence in instrument handling, 80% in cable knot tying and 70% in suture tying. Overall student rating for the virtual surgical skills session was 8.85 (±1.19) out of 10 (10 being most satisfied). Conclusions: We demonstrate that successful delivery of a virtual ophthalmic surgical skills course is feasible. We were able to widen accessibility and participation through virtual delivery, which has future implications for ophthalmic surgical teaching and its reach

Effectiveness of adjuvant photoactivated chromophore corneal collagen cross-linking versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of adjuvant photoactivated chromophore for keratitis - corneal collagen cross-linking (PACK-CXL) versus standard antimicrobial treatment alone for corneal healing in patients with infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause for corneal blindness globally. Broad-spectrum antimicrobial therapy is currently the standard treatment, but there is a growing need for alternative or adjuvant antimicrobial treatment, due to the emerging antimicrobial resistance, long treatment duration and cost of treatment. Photoactivated chromophore for keratitis - corneal collagen cross-linking has been increasingly used as an adjuvant treatment for infectious keratitis but high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients with infectious keratitis, encompassing bacterial, fungal, acanthamoeba, viral, mixed or culture-negative presumed infectious keratitis cases. Patients who have a previous history of infectious keratitis before the study or those that had less than seven days' follow-up from the start of the treatment will be excluded. METHODS: The electronic databases to be searched will include MEDLINE, Embase and Cochrane Central Register of Controlled Trials. Only English articles will be included. Titles, abstracts and full text of the relevant studies will be assessed by two independent reviewers. The extracted data will include specific details about the study, including authors and study title, year of publication, sample size, populations, and study methods. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities in the reporting of outcome measures. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019131290

Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis

Infectious keratitis (IK) is the 5th leading cause of blindness globally. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though adjuvant treatment or surgeries are often required in refractory cases of IK. This systematic review aimed to examine the effectiveness and safety of adjuvant amniotic membrane transplantation (AMT) for treating IK. Electronic databases, including MEDLINE, EMBASE and Cochrane Central, were searched for relevant articles. All clinical studies, including randomized controlled trials (RCTs), non-randomized controlled studies and case series (n > 5), were included. Primary outcome measure was time to complete corneal healing and secondary outcome measures included corrected-distance-visual-acuity (CDVA), uncorrected-distance-visual-acuity (UDVA), corneal vascularization and adverse events. A total of twenty-eight studies (including four RCTs) with 861 eyes were included. When compared to standard antimicrobial treatment alone, adjuvant AMT resulted in shorter mean time to complete corneal healing (- 4.08 days; 95% CI - 6.27 to - 1.88; p < 0.001) and better UDVA (- 0.26 logMAR; - 0.50 to - 0.02; p = 0.04) at 1 month follow-up in moderate-to-severe bacterial and fungal keratitis, with no significant difference in the risk of adverse events (risk ratio 0.80; 0.46-1.38; p = 0.42). One RCT demonstrated that adjuvant AMT resulted in better CDVA and less corneal vascularization at 6 months follow-up (both p < 0.001). None of the RCTs examined the use of adjuvant AMT in herpetic or Acanthamoeba keratitis, though the benefit was supported by a number of case series. In conclusion, AMT serves as a useful adjuvant therapy in improving corneal healing and visual outcome in bacterial and fungal keratitis (low-quality evidence). Further adequately powered, high-quality RCTs are required to ascertain its therapeutic potential, particularly for herpetic and Acanthamoeba keratitis. Future standardization of the core outcome set in IK-related trials would be invaluable

Effectiveness and safety of early adjuvant amniotic membrane transplant versus standard antimicrobial treatment for infectious keratitis: a systematic review protocol

OBJECTIVE: The objective of this review is to systematically examine the effectiveness of early adjuvant amniotic membrane transplant versus standard antimicrobial therapy for infectious keratitis. INTRODUCTION: Infectious keratitis is a major cause of corneal blindness worldwide. Broad-spectrum topical antimicrobial therapy is currently the gold standard for treatment. Amniotic membrane transplant has been employed as an adjuvant therapy to promote corneal healing; however, high-quality evidence is limited. INCLUSION CRITERIA: This review will consider studies that include patients of all ages with all types of infectious keratitis, including bacterial, fungal, viral, acanthamoeba, mixed, and culture-negative presumed infectious keratitis. The authors will exclude patients who have undergone other types of primary surgery other than amniotic membrane transplant during the initial management and those who had less than seven days' follow-up from the commencement of the treatment. METHODS: Electronic databases, including MEDLINE, Embase, Cochrane CENTRAL, and relevant registries, will be searched for pertinent studies. Titles, abstract, and full text of the relevant studies will be independently assessed by two reviewers. Extracted data will include authors, year of publication, sample size, types of amniotic membrane transplant techniques, types of causative microorganisms, main outcomes, visual acuity, and adverse events. No restriction will be applied to the date or language. Bibliographies of the included articles will be independently and manually screened by two authors to identify further relevant studies. Eligible studies will be critically appraised by two independent reviewers for methodological quality. A meta-analysis will be performed for the included randomized controlled trials when there are sufficient similarities. SYSTEMATIC REVIEW REGISTRATION NUMBER: This systematic review has been registered with PROSPERO (CRD42020175593)

Corneal endothelial cell density loss following glaucoma surgery alone or in combination with cataract surgery: a systematic review protocol

Objective: We aim to systematically assess and compare corneal endothelial cell density (ECD) loss in patients with glaucoma following glaucoma surgery and cataract surgery. / Introduction: Corneal ECD loss may occur due to intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. Corneal oedema and decompensation after aqueous shunt glaucoma surgery has been reported but the long-term ECD loss is still unknown. / Inclusion criteria: Trabeculectomy, glaucoma filtration surgery or microinvasive glaucoma surgery in adults with ocular hypertension, primary and secondary open angle glaucoma, normal tension glaucoma and angle-closure glaucoma. Participants with pre-existing corneal disease will be excluded. Glaucoma laser treatments and peripheral iridotomy will be excluded. The outcomes include preoperative and postoperative corneal ECD, percentage change of corneal ECD and adverse events. / Methods: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and The International Prospective Register of Systematic Reviews (PROSPERO). Eligibility criteria will include quantitative articles published after and including the year 2000, written in English and containing data on ECD loss. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using the Joanna Briggs Institute critical appraisal forms. / Ethics and dissemination: Ethics approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. / PROSPERO registration number: PROSPERO CRD42020192303

Preclinical challenges for developing long acting intravitreal medicines

The majority of blinding conditions arise due to chronic pathologies in the retina. During the last two decades, antibody-based medicines administered by intravitreal injection directly into the back of the eye have revolutionised the treatment of chronic retinal diseases characterised by uncontrolled blood vessel growth, e.g. wet age-related macular degeneration (wAMD), diabetic retinopathy (DR) and choroidal neovascularisation. Although intravitreal injections have become a commonly performed ophthalmic procedure that provides a reproducible dose to maximise drug exposure in the back of the eye, there is a need to minimise the frequency and cumulative number of intravitreal injections. Developing longer-acting intraocular therapies is one key strategy that is being pursued. Pharmaceutical preclinical development of intraocular medicines is heavily reliant on the use of animal models to determine ocular tolerability, pharmacokinetics, biodistribution and drug stability. Animal eyes are different from human eyes, such as the anatomy, organisation of vitreous macromolecular structure, aqueous outflow and immune response; all which impacts the ability to translate preclinical data into a clinical product. The development of longer acting protein formulations using animals is also limited because animals reject human proteins. Preclinical strategies also do not account for differences in the vitreous due to ageing and whether a vitrectomy has been performed. Intraocular formulations must reside and clear from the vitreous body, so there is a need for the formulation scientist to have knowledge about vitreous structure and physiology to facilitate preclinical development strategies. Preclinical pharmaceutical development paradigms used to create therapies for other routes of administration (e.g. oral and intravenous) are grounded on the use of preclinical in vitro models. Analogous pharmaceutical strategies with appropriately designed in vitro models that can account for intraocular mass transfer to estimate pharmacokinetic profiles can be used to develop in vitro-in vivo correlations (IVIVCs) to accelerate the preclinical optimisation of long acting intraocular formulations. Data can then inform preclinical in vivo and clinical studies. With the now widespread use of intravitreal injections, it has also important early in preclinical studies to ensure there is a viable regulatory pathway for new therapies. Knowledge of these factors will help in the development of long acting intravitreal medicines, which is rapidly evolving into a distinct pharmaceutical discipline