Benefits and risks of orthokeratology treatment: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis reviews the evidence for the risks and benefits associated with orthokeratology (OK) treatment compared with other methods of myopia control in children and adults. METHODS: A systematic search of Cochrane Central Register of Controlled Trials, Pubmed, Embase and Ovid was conducted from database inception to 22nd August 2021. Studies that reported on risks, visual and ocular biometric effects of OK in patients > 5 years of age with myopia (- 0.75 to - 6.00D) were included. Main outcomes are change in axial length and any adverse event. RESULTS: Fourty-five papers were included in this systematic review and meta-analysis. The quality of data was variable and of moderate certainty, and selection bias likely skewed the results towards a relative benefit for OK. The rate of axial elongation in children was lower for OK treatment compared to other treatment modalities at one year (MD - 0.16 mm, 95% CI - 0.25 to - 0.07). Rate of change in axial length in children rebounded after OK discontinuation compared to participants who continued treatment (MD 0.10 mm, 95% CI 0.06 to 0.14). Adults and children wearing OK were up to 3.79 times more likely to experience an adverse event when compared with conventional contact lenses (OR 3.79, 95% CI 1.24 to ll.), though this evidence base is underdeveloped and requires additional well-designed studies for substantial conclusions to be drawn. CONCLUSIONS: OK arrests myopia progression while in use, however, there remain unanswered questions about the optimal duration of treatment, discontinuation effects and long-term risk for adverse events.

Biologics in peripheral ulcerative keratitis.

Over the past two decades biologic therapies have seen a rapid uptake in the management of ocular inflammation. Peripheral ulcerative keratitis (PUK), once a harbinger of blindness and mortality in refractory rheumatological disease, is now increasingly being treated with these agents. We conducted a review to evaluate the evidence base for this application and to provide a road map for their clinical usage in PUK, including dosage and adverse effects. A literature search across Medline, Embase and Cochrane Database of Systematic Reviews was undertaken to identify all patients with PUK that were treated with a biologic in a peer viewed article. Overall, whilst the evidence base for biologic use in PUK was poor, reported cases demonstrate an increasingly powerful and effective role for biologics in refractory PUK. This was particularly the case for rituximab in PUK secondary to granulomatous with polyangiitis.

Closed globe and adnexal eye injuries: Epidemiology, clinical and surgical outcomes, and an economic cost analysis.

BACKGROUND: To examine the epidemiology, visual outcomes, surgical interventions, and socioeconomic costs of closed globe (CGI) and adnexal injuries. METHODS: A retrospective 11-year tertiary-trauma centre study of 529 consecutive CGI was conducted using the Revised Globe and Adnexal Trauma Terminology classification in individuals aged ≥16 years. Outcome measures included best-corrected visual acuity (BCVA), operating theatre visits, and socioeconomic costs. RESULTS: CGI disproportionately impacted young males during work (89.1%) and sports (92.2%), with eye protection only worn in 11.9% and 2.0%, respectively. Home was the most prevalent location (32.5%) due to falls (52.3%) in older females (57.9%). Concomitant adnexal injuries occurred frequently (71.5%), particularly in assaults (88.1%), and included eyelid lacerations (20.8%), orbital injuries (12.5%), and facial fractures (10.2%). Final median BCVA improved to 0.2 logMAR [6/9] (IQR 0-0.2) from 0.5 logMAR [6/18] (IQR 0-0.5) (p < 0.001). Surgery was required in 89 CGI (16.8%) in 123 theatre visits. In multivariable logistical regression modelling, presenting BCVA was predictive of final BCVA (odds ratio [OR] 8.4, 95% confidence interval [95%CI] 2.6-27.8, p < 0.001), while involvement of the lids (OR 2.6, 95%CI 1.3-5.3, p = 0.006), nasolacrimal apparatus (OR 74.9, 95%CI 7.9-707.4, p < 0.001), orbit (OR 5.0, 95%CI 2.2-11.2, p < 0.001), and lens (OR 8.4, 95%CI 2.4-29.7, p < 0.001) predicted for operating theatre visits. Economic costs totalled AUD20.8-32.1 million (USD16.2-25.0 million) and were estimated at AUD44.5-77.0 million (USD34.7-60.1 million) annually for Australia. CONCLUSIONS: CGI is a prevalent and preventable burden on patients and the economy. To mitigate this burden, cost-effective public health strategies should target at-risk populations.

Epidemiology and Economic Cost Analysis of Microbial Keratitis from a Tertiary Referral Hospital in Australia.

Microbial keratitis is the most common cause of infective vision loss. The causative organism varies by region, and most cases require intensive antimicrobial therapy. The purpose of this study was to analyse the causative organisms of microbial keratitis, its presentation and economic burden from a tertiary referral hospital in Australia. A retrospective review of 160 cases of microbial keratitis was performed, over a 5-year period from 2015-2020. A wide variety of costs were considered to determine the economic burden, using standardized data from the Independent Hospital Pricing Authority and the cost of personal income loss. Our study showed the most commonly occurring pathogens were Herpes Simplex (16%), Staphylococcus aureus (15.1%) and Pseudomonas aeruginosa (14.3%). A total of 59.3% of patients were admitted, with a median length of admission of 7 days. Median cost for all presentations of microbial keratitis was AUD 8013 (USD 5447), with costs significantly increasing with admission. The total annual cost of microbial keratitis within Australia is estimated to be AUD 13.58 million (USD 9.23 million). Our findings demonstrate that microbial keratitis represents a significant economic burden for eye-related diseases and the key driving factor for the cost is the length of admission. Minimizing the duration of admission, or opting for outpatient management where appropriate, would significantly reduce the cost of treatment for microbial keratitis.

Ocular streptococcal infections: A clinical and microbiological review.

Streptococcus is a diverse bacterial genus that is part of the ocular surface microbiome implicated in conjunctivitis, keratitis, endophthalmitis, dacryocystitis, and orbital cellulitis that can lead to decreased visual acuity and require surgical intervention. The pathophysiology of S. pneumoniae is well-established and the role of the polysaccharide capsule, pneumolysin, neuraminidases, and zinc metalloproteinases in ocular infections described. Additionally, key virulence factors of the viridans group streptococci such as cytolysins and proteases have been outlined, but there is a paucity of research on the remaining streptococcus species. These virulence factors tend to result in aggressive disease. Clinically, S. pneumoniae is implicated in 2.7-41.2% of bacterial conjunctivitis cases, more predominant in the pediatric population, and is implicated in 1.8-10.7% of bacterial keratitis isolates. Streptococcus bacteria are significantly implicated in acute postoperative, postintravitreal, and bleb-associated endophthalmitis, responsible for 10.3-37.5, 29.4, and 57.1% of cases, respectively. Group A and B streptococcus endogenous endophthalmitis is rare, but has a very poor prognosis. Inappropriate prescription of antibiotics in cases of nonbacterial aetiology has contributed to increasing resistance, and a clinical index is needed to more accurately monitor this. Furthermore, there is an increasing need for prospective, surveillance studies of antimicrobial resistance in ocular pathogens, as well as point-of-care testing using molecular techniques.

Minimally invasive, indirect corneal neurotization using an ipsilateral sural nerve graft for early neurotrophic keratopathy.

Purpose: Neurotrophic keratopathy is a degenerative disease characterized by damage to the corneal nerves leading to corneal hypoesthesia and anaesthesia. The resultant progressive visual deterioration is refractory to existing conventional treatment options. Corneal neurotization is a novel and effective surgical procedure that directly targets the underlying pathology of nerve loss by stimulating new corneal nerve growth. This study reports the outcomes and the pre- and postoperative in vivo confocal microscopy findings of the first published Australian case of indirect, minimally invasive, corneal neurotization using an ipsilateral sural nerve autograft. Observations: An 11-year-old boy developed corneal hypoesthesia in the left eye following surgical debulking of a cerebellopontine angle arachnoid cyst. He was diagnosed with Mackie Stage 1 neurotrophic keratopathy. Due to his hypoesthesia, he had developed recurrent microbial keratitis and corneal ulceration secondary to foreign bodies sustained during contact sports. At presentation, he reported photophobia and dry eye symptoms, corrected-distance visual acuity was 6/18, Cochet-Bonnet aesthesiometer demonstrated reduced corneal sensation (5-15mm), Schirmer's I test was 15mm, and in vivo confocal microscopy showed a complete absence of a subepithelial corneal plexus. He underwent indirect, minimally invasive, corneal neurotization using the ipsilateral supratrochlear nerve and a sural nerve autograft. Subjective improvement in corneal sensation was noticed by the patient at 2 months. Objective improvement, measured on Cochet-Bonnet aesthesiometer, was first observed at 6 months with steady stepwise improvement to 20-35mm at 21 months. Importantly, due to the increase in corneal sensation, the patient did not develop any further corneal complications. At 12 months, dry eye symptoms resolved and Schirmer's I test improved to 30mm. At 15 months, corrected-distance visual acuity improved to 6/5 and in vivo confocal microscopy demonstrated evidence of corneal reinnervation with nerves running through the subepithelial space surrounded by healthy and active keratocytes. Conclusions and importance: Corneal neurotization represents an exciting development in the armamentarium for the treatment of neurotrophic keratopathy and can be considered for younger patients with early-stage disease.

Determining the learning curve for a novel microsurgical procedure using histopathology.

PURPOSE: Wet laboratories are becoming an increasingly important training tool as part of a push to a proficiency-based training model. We created a microsurgical wet laboratory to investigate the utility of histopathology use in assessing surgical outcomes and determine the learning curve of a novel microsurgical procedure. METHODS: A microsurgical wet laboratory was established using pig eyes to simulate the human cornea. Three novice surgeons and an experienced surgeon performed an anterior cornea lamellar dissection and the duration of the procedure was recorded. With the aid of histological analysis, the thickness and characteristics of the dissected graft was recorded. The number of attempts to complete the experiment, defined as three successful dissections with mean thickness below 100 µm, was documented. RESULTS: The use of histopathology was highly successful allowing in-depth analysis of the dissected graft for each attempt. Trainees reached the endpoint of the study in 21, 26 and 36 attempts (mean: 28 attempts) whilst the corneal surgeon completed the experiment in 12 attempts (p = 0.07). Mean dissection thickness decreased over time for all participants. The mean dissection time for trainees was 10.6 ± 4.2 min compared to the corneal surgeon with a mean of 8.2 ± 3.1 min (p = 0.03). CONCLUSION: We propose a corneal wet laboratory model that allows for simple, efficient, and flexible microsurgical training. The use of histopathological analysis allows for careful graft analysis, providing objective feedback throughout the training exercise. Trainees demonstrated improvements in the three key aspects of the procedure: accuracy as evidenced by decreasing histological thickness, confidence by self-report and fluidity by decreasing duration of the procedure.

Ocular Distribution of the Renin-Angiotensin-Aldosterone System in the Context of the SARS-CoV-2 Pandemic.

The COVID-19 pandemic has resulted in an unprecedented impact on global health, economy, and way of life. SARS-CoV-2, the virus responsible for the disease, utilizes the ACE2 receptor found on host cells to mediate entry, replication, and infection. Numerous studies have elucidated the presence of many components of the renin-angiotensin-aldosterone system (RAAS) in the eye, including the ACE2 receptor. Considering this, and the anatomical vulnerability that the exposed ocular surface offers with its interconnectedness to the respiratory system, there is a theoretical risk of pathogen entry from the ocular route as well as the development of COVID-19-associated eye disease. Despite this, the actual epidemiological data demonstrates low ocular symptoms, possibly due to differing ACE2 receptor expression across age, ethnicity, and sex coupled with the protective properties of tears. We summarize the current literature on ocular RAAS with specific focus on the ACE2 receptor and its interplay with the SARS-CoV-2 virus.

Open globe injuries: Epidemiology, visual and surgical predictive variables, prognostic models, and economic cost analysis.

BACKGROUND: Open globe injuries (OGI) represent a visually and economically devastating cause of vision loss. We examined the epidemiology, predictive variables, prognostic models, and economic cost of surgically managed OGI. METHODS: A retrospective tertiary centre study from 2008 to 2018 of 155 consecutive OGI in individuals aged 16 and older was performed. Medical records review, application of Ocular Trauma Score (OTS) and Classification and Regression Tree Analysis (CART) and cost analysis were undertaken. Key outcomes measured were visual acuity, number of operating theatre visits, prognostication using OTS and CART and estimated costs. RESULTS: Younger males at work with inadequate protective eyewear (89.1%) and falls in the elderly were overrepresented. Inferior visual outcomes were associated with a more severe OTS score, a larger injury zone, increasing age, the presence of retinal detachment, extraocular muscle involvement, intraocular foreign body, and globe rupture (R2  = 0.723, p < 0.001). Multiple operating theatre visits were required in the presence of retinal detachment, lens or orbit involvement, work-related injury, globe rupture, and a history of previous intraocular surgery (R2  = 0.0423, p < 0.001). Both OTS and CART prognosticated outcomes (p < 0.001). The OTS predicted for no vision (no light perception/enucleation/evisceration) and profound visual loss (worse than 6/120; specificity: both 100%, sensitivity: 88.2% and 88%) whereas the CART predicted for visual survival (light perception or better) and minimal-to-severe visual loss (6/120 or better; specificity: 88.5% and 81.7% , sensitivity: 97.7% and 100%). Estimated annual OGI cost for Australia was AUD48.1-60.5 million (USD37.3-47.0 million). CONCLUSIONS: The total cost of OGI is immense with young males and the elderly being disproportionately affected. Implementation of targeted government legislation and public health preventative measures may be cost-effective in ameliorating the significant burden.

LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation.

Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required-particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs.

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia.

PURPOSE: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia. METHODS: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline. RESULTS: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources. CONCLUSIONS: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Local delivery of corticosteroids in clinical ophthalmology: A review.

Locally administered steroids have a long history in ophthalmology for the treatment of inflammatory conditions. Anterior segment conditions tend to be treated with topical steroids whilst posterior segment conditions generally require periocular, intravitreal or systemic administration for penetration. Over recent decades, the clinical applications of periocular steroid delivery have expanded to a wide range of conditions including macular oedema from retino-vascular conditions. Formulations have been developed with the aim to provide practical, targeted, longer-term and more efficacious therapy whilst minimizing side effects. Herein, we provide a comprehensive overview of the types of periocular steroid delivery, their clinical applications in ophthalmology and their side effects.

The Impact on Work Patterns of Implementing the Save Sight Keratoconus Registry in the Hospital Setting.

PURPOSE: The adoption of clinical registries has the potential to improve outcomes, while reducing the costs of health care. We sought to evaluate the changes in workflow that occurred with implementation of the Save Sight Keratoconus Registry (SSKR) in corneal clinics. METHODS: A prospective time-motion study and a clinician survey were conducted. The timing of clinic consultations was recorded before and after implementation of the SSKR. The activities were assigned into 3 main categories: 1) direct patient care (eg, talking to, examining), 2) indirect patient care (record keeping), and 3) indirect patient care (reading). RESULTS: Overall, there was no change in average time spent per patient with or without the SSKR; 12.3 (5.3 SD) versus 12.1 (5.3 SD) minutes, respectively, P = 0.84. There was no change in time spent providing direct care with or without the SSKR; 5.4 (2.8 SD) versus 5.9 (2.8 SD) minutes, respectively, P = 0.51. Within direct patient care, there was no impact with or without the SSKR on the time spent examining (1.9 [1.0 SD] vs. 1.9 [1.4 SD] minutes, respectively, P = 0.58) or talking to patients (3.5 [2.3 SD] vs. 4.1 [2.3 SD] minutes, respectively, P = 0.21). Indirect care time was unchanged overall for record keeping (3.2 [2.2 SD] vs. 4.6 [2.9 SD], respectively, P = 0.16) and reading tasks (3.1 [1.8 SD] vs. 2.0 [1.3 SD], respectively, P = 0.09). CONCLUSIONS: The SSKR was implemented into clinical practice without affecting the total consultation time, time spent directly interacting with patients, or use of patient records. Our findings support that registries requiring data entry could be widely adopted into routine clinical practice.

Optic nerve sheath meningiomas: prevalence, impact, and management strategies.

Optic nerve sheath meningiomas are rare benign neoplasms of the meninges surrounding the optic nerve. They are a significant cause of morbidity. While the mortality rate is practically zero, these tumors can blind or disfigure patients. Given that the clinical course can be variable, and treatment has the capacity to cause morbidity itself, the management of these patients can be difficult. We review the literature to discuss the prevalence of optic nerve sheath meningiomas, the association with neurofibromatosis type 2, natural history, and management options and strategies.

Boston keratoprosthesis type 1: outcomes of the first 38 cases performed at Moorfields Eye Hospital.

PURPOSE: To evaluate outcomes of Boston keratoprosthesis type 1 (K-Pro) surgery in a cohort of high-risk patients at Moorfields Eye Hospital. Our patients were referred to us at the end-point of their ocular disease. METHODS: A retrospective review of all K-Pro surgery performed between March 2011 and July 2015 with a minimum follow-up of 12 months. RESULTS: 39 eyes of 38 patients were included. Mean follow-up was 28.4 months (range: 12-56). The main indication for surgery was bullous keratopathy from multiple failed grafts (56%). 26 cases (72.2%) had known posterior segment disease pre-operatively. Mean BCVA for the entire cohort (n = 39) initially improved from HM vision to 1/60 before returning to CF vision by 6 months and was maintained for the duration of follow-up. By final follow-up (n = 39), 46% had improved vision (1 line improvement in 10%; 2 lines or more in 36%) and 31% maintained pre-operative visual acuity. Anterior segment pathology was not an independent variable in visual outcome. However, absence of posterior segment disease was significant and performed best, improving from HM to 6/15 and maintaining that vision in the longer term. There were 13 (33%) cases of progressive glaucomatous optic neuropathy, 10 (26%) retinal detachments, 8 (21%) retroprosthetic membranes, 3 (8%) infective keratitis and 2 (5%) vitritis of which 1 progressed to endophthalmitis. In all, 3 (8%) had NPL vision and 4 (10%) required removal of the K-Pro. CONCLUSIONS: Implantation of the Boston K-Pro can lead to improved vision, with the main limiting factor being posterior segment pathology.

Dendritic cells in the cornea during Herpes simplex viral infection and inflammation.

Herpes simplex keratitis is commonly caused by Herpes simplex virus type 1, which primarily infects eyelids, corneas, or conjunctiva. Herpes simplex virus type 1-through sophisticated interactions with dendritic cells (DCs), a type of antigen-presenting cell)-initiates proinflammatory responses in the cornea. Corneas were once thought to be an immune-privileged region; however, with the recent discovery of DCs that reside in the cornea, this long-held conjecture has been overturned. Therefore, evaluating the clinical, preclinical, and cell-based studies that investigate the roles of DCs in corneas infected with Herpes simplex virus is critical. With in vivo confocal microscopy, animal models, and cell culture experiments, we may further the understanding of the sophisticated interactions of Herpes simplex virus with DCs in the cornea and the molecular mechanism associated with it. It has been shown that specific differentiation of DCs using immunohistochemistry, flow cytometry, and polymerase chain reaction analysis in both human and mice tissues and viral tissue infections are integral to increasing understanding. As for in vivo confocal microscopy, it holds promise as it is the least invasive and a real-time investigation. These tools will facilitate the discovery of various targets to develop new treatments.

Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations.

PURPOSE: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. METHODS: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-µm thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. RESULTS: Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 µm hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3/10) cases. CONCLUSIONS: An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.