Elsie W. Chan

Refractive lens exchange (RLE) currently dominates the refractive surgery landscape ahead of laser vision correction (LVC) and phakic intraocular lenses (pIOLs), with the 2022–23 EUROQUO Annual Report finding that RLE represented 80% of reported refractive surgery cases [1]. However, the evidence base for RLE in the management of high ametropia is limited - well conducted, comparative studies cannot be performed due to ethical issues in case selection and treatment allocation. Instead, we must use results from retrospective studies on RLE and infer risks from cataract surgery data to determine whether RLE is the appropriate option for refractive patients. Expectations are high in this cohort, but outcomes following RLE are not well published. Hannan et al. reported a large series of immediate, sequential, bilateral RLE cases from the United Kingdom (34,660 eyes, mean age 56.95 years, 78.6% low hypermetropes and 83.2% multifocal IOLs [MFIOL]) where 86.2% of eyes receiving MFIOLs were within 0.5D of intended refraction [2]. However, only 42.9% had a post-operative uncorrected distance visual acuity (UDVA) which was the same or better than their pre-operative corrected visual acuity (CDVA). While this is favourable to the EUROQUO large cataract dataset reporting 75% of eyes within 0.5D of intended refraction [1], the results are not 100%, and this must be factored into pre-operative counselling. There are also no recent, large studies comparing different IOLs in young RLE patients. A meta-analysis by Rosen et al. from 2016 reported that UDVA did not significantly differ between patients who had cataract surgery compared to RLE, suggesting that it is reasonable to extrapolate results on IOL outcomes in cataract surgery to the RLE cohort when exploring options with patients [3]. Presbyopic hypermetropes are considered the ideal candidates for RLE. Conversely, in pre-presbyopic hypermetropes, LVC or pIOLs are better suited to maintain accommodation. There are limited publications on RLE in pre-presbyopic hypermetropes. Djodeyre et al. reported on 133 young high hypermetropes (mean spherical equivalent +6.29D, mean age 36.94 years) who underwent bilateral RLE with a MFIOL [4]. 92% were within 0.5D of target and 89% of eyes had the same or better post-operative UDVA compared to pre-operative CDVA. Importantly, 97% of patients reported satisfaction with the outcome and 100% reported spectacle independence at all distances. Due to the risk of vitreoretinal complications, RLE is less commonly performed in pre-presbyopic myopic eyes, and therefore publications on outcomes in this group is limited. Instead, LVC or pIOLs may be preferred. In the setting of a presbyopic myope with pre-existing posterior vitreous detachment (PVD) however, RLE may be cautiously considered. Brenner et al. reported the results of RLE in 35,206 eyes with a trifocal IOL, where 8118 (23.4%) were myopic (mean spherical equivalent −3.62D, mean age 53.0 years) [5]. Compared to the emmetropic and hypermetropic groups, there were no differences in UDVA, binocular UDVA or binocular uncorrected near visual acuity between the three groups. Enhancement surgery was performed in 12–20% of patients, depending on the IOL formula used. Retinal detachments are a feared post-operative complication of RLE. It is postulated that pseudophakic RD occurs as the reduction in lens volume draws the anterior hyaloid face forward, with vitreous base traction resulting in retinal breaks. Pseudophakia may also alter vitreous protein composition, accelerating syneresis that leads to PVD [6]. Our knowledge of RD rates after lens extraction largely comes from the cataract population data; the overall 10-year incidence of RD following cataract surgery is between 0.36 and 2.9%, which is 10 times the general population risk [7]. The Swedish National Cataract Register followed up 58,624 cataract surgeries over a mean follow-up period of 4.67 years and reported 0.51% RDs [8]. The mean time to RD was 1.83 years following surgery. This is longer than the follow-up period of most RLE and cataract studies, highlighting the need for longer-term outcome data. Increasing axial length and younger age were strong risk factors for RD (Table 1), in addition to vitreous loss and male sex. Combining these risks, in patients younger than 60 years with an axial length greater than 25 mm, the incidence of a RD was 6.40% within the follow-up period, which increased to 9.46% in male patients. Notably, the risk for RD was not stratified by PVD status in this study. The United States based IRIS® registry (Intelligence Research in Sight) also reported on RD following cataract surgery [9]. Additional risk factors included presence of lattice degeneration (multivariable odds ratio 10.53) and new onset of PVD following surgery (odds ratio 1.24). Table 1 Incidence of retinal detachment following cataract surgery during the study period (mean 4.67 years) from the Swedish National Cataract Register [8]. Full size table As many risk factors for a RD are not modifiable, accurate pre-operative assessment of a PVD in myopes is important. Kičová et al. compared techniques to identify the presence of a complete PVD, and found the most accurate was B-scan ultrasonography with an experienced operator (83% accuracy) followed by clinical examination (76% accuracy) [10]. Macular optical coherence tomography (OCT) is useful for ruling out PVD when an attached posterior hyaloid is visualised, but the converse is not true; the absence of visible hyaloid on macula OCT does not confirm a complete, peripheral PVD [11]. It is also worth noting that the presence of a complete PVD reduces but does not eliminate RD risk; even vitrectomised eyes can develop RD after lens surgery [12, 13]. The MYOPRED (Influence of PVD on retinal detachment after lens surgery in myopic eyes) study seeks to further investigate this issue in high myopes undergoing lens surgery over a 5-year follow-up period [14]. The consequences of posterior capsule opacification (PCO) should also be considered. High myopes appear to have increased rates of post-capsulotomy RD [15], which is thought to occur via disruption of the anterior hyaloid face or acoustic trauma to the vitreous base [16]. This is relevant in RLE as a younger age increases the risk of PCO [17, 18]; the PCO rate was 7.89% in Djodeyre et al.’s RLE study [3]. The limited evidence from RLE case series and extrapolation from cataract surgery data suggest RLE has favourable outcomes and an acceptable safety profile, especially in high hypermetropia. The role of RLE in myopia is less clear, particularly in presbyopic high myopes without PVD, where RLE may improve unaided visual acuity, but may introduce vitreoretinal pathology, sometimes years later. Understanding PVD status and considering alternatives may be more appropriate in this at-risk cohort. Furthermore, a small number of patients will lose distance acuity following RLE. Appropriate patient counselling is, therefore, essential.

Background: To identify evidence on the use of topical CsA for ocular surface diseases (OSD). Methods: A literature search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) through June 2023 via Cochrane Central Registries, Clinical Trials Registry, Grey literature and citation searching. Randomised clinical trials (RCTs) in which different concentrations of topical CsA were compared with one another or other topical therapies were included. Risk of bias was assessed following the Cochrane ROB2 standard tool. Meta-analysis was considered when data were sufficient. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results: Five hundred and eight-three RCT publication titles were identified, of which 48 OSD RCTs were included. Thirty trials found significantly better efficacy with CsA irrespective of dose or concentration for OSD. The effect of CsA was comparable to artificial tears (AT), vehicle, fluorometholone 0.1%, tacrolimus 0.03% or diquafosol 3% only in 13 trials. Improved outcomes with CsA for symptoms (RCTs comprising 1107-patients) and clinical signs, including in ocular surface staining (2505-patients) and the average number of goblet cells (138-patients) were found. Inconsistency of treatment effect on symptoms and signs, particularly tear film function, was evident in some trials. Ten trials were judged to be at high risk of bias. The certainty of evidence was judged to be low to moderate, downgraded mostly for imprecision and risk of bias. Conclusions: Topical CsA treatment effect on ocular surface symptoms and staining suggests that CsA may be superior to the vehicle, AT or other topical treatment alternatives for OSD.

Objective: We report a unique case of significant human papillomavirus-associated conjunctival papillomas and severe corneal ulceration leading to corneal perforation in a patient treated with dupilumab for atopic dermatitis. Methods: This study is a case report and literature review of severe corneal side effects related to dupilumab. Results: A 27-year-old man with severe atopic dermatitis and no ocular history was administered dupilumab 300 mg via subcutaneous injections every 2 weeks with an excellent response. Following the onset of treatment, the patient developed conjunctivitis, conjunctival papillomas, and dry eyes, which were initially treated with lubricating eye drops. Fourteen months after commencing dupilumab, he had a rapid onset of painful visual loss in the OD accompanied by severe bilateral conjunctival injection and was found to have a central corneal ulcer and diffuse papillomas on the palpebral and bulbar conjunctiva. Despite management with intravenous methylprednisolone and topical dexamethasone, the patient's corneal ulcer progressed to a corneal melt, resulting in perforation 2 months after diagnosis, which necessitated a corneal graft. Conclusions: We present the third reported case of dupilumab-associated corneal perforation and the first case to our knowledge of dupilumab-associated conjunctival papillomas. As dupilumab usage increases, awareness of these potential complications among prescribers is essential.

Objective: This study evaluates the performance of a multitrait polygenic risk score (PRS) in an independent cohort to predict incident or progression of keratoconus. Methods: Prospective cross-sectional and cohort study METHODS: Setting: Single-center; Study population: 1478 community-based young adults (18-30 years; 51% female), including 609 (52% female) who returned for an 8-year follow-up; Observation procedures: Scheimpflug imaging (Pentacam, Oculus), genotyping and development of a multitrait PRS previously validated to predict keratoconus in older adults.; Main outcome measure: Belin/Ambrόsio enhanced ectasia display (BAD-D) score and keratoconus, defined as BAD-D ≥2.6, were each analyzed against the PRS using linear and logistic regression, respectively. Results: Prevalence of keratoconus was 2.5% (95% confidence interval [CI] = 1.9-3.6) in the cross-sectional cohort. Each z-score increase in PRS was associated with worse BAD-D z-score by 0.13 (95%CI = 0.08-0.18) and 1.6 increased odds of keratoconus. The 8-year keratoconus incidence was 2.6% (95%CI = 1.3-4.0). Participants in the highest PRS decile were more likely to have incident keratoconus compared to the rest of the cohort (odds ratio = 3.85, 95%CI = 1.21-12.22). For each z-score increase in PRS, 8-year change in BAD-D z-score worsened by 0.11 (95%CI = 0.04-0.17). Conclusions: A PRS for keratoconus could be useful in predicting incident keratoconus and progression, demonstrating its potential utility in clinical settings to identify patients at high risk of postsurgery ectasia or those who may benefit most from keratoconus intervention.

This review discusses the current practices, attitudes, and trends in diagnosing and managing keratoconus (KC) in adults and children by optometrists and ophthalmologists in order to highlight the differences on a global scale. Two independent reviewers searched the electronic databases and grey literature for all potential articles published from 1 January 2000 to 1 June 2022 on management of KC. Keywords used in searches included "keratoconus", "diagnosis", "management", "treatment", "attitude", "practices", "opinion", "optometrist", "ophthalmologist", "consensus", and "protocol". A total of 19 articles was included in this review-12 from the database search and seven from the grey literature. Although a common stepwise approach of non-surgical management was noted, there were differences in the rates of prescribing rigid gas permeable lenses. Furthermore, while clinicians agreed on the need for early diagnosis, the timeline and type of referral varied significantly. A similar discordance was found in the milestones for surgical intervention and preferred surgical techniques. Practice patterns in keratoconus diagnosis and management vary throughout the world. Multiple recommendations and suggestions to minimise the differences have been provided in the literature, with the main themes being improvement in education, interdisciplinary patient care, and further research to reach consensus.