A Standardized Protocol of Simultaneous Transepithelial Phototherapeutic Keratectomy (PTK) Followed by Corneal Collagen Crosslinking for Keratoconus.

PURPOSE: To report outcomes in patients with progressive keratoconus who underwent a standardized protocol of transepithelial phototherapeutic keratectomy (t-PTK) laser followed by accelerated corneal collagen crosslinking (CXL). METHODS: All patients with progressive keratoconus undergoing our protocol at a London clinic between 2019 and 2023 were included. The protocol involved t-PTK at 58-µm central ablation depth at a 9-mm treatment zone on the Schwind Amaris 1050RS platform. Preoperative K readings of 43.0D (both K1 and K2) were inputted for all cases. Patients then underwent CXL with a pulsed-light accelerated protocol (30 mW/cm2 for 8 minutes of UVA exposure time with 1 second on/1 second off). RESULTS: Seventy-nine eyes from 55 patients were included with an average follow-up of 12 months (range 6-24 months). Both mean uncorrected distance visual acuity (UDVA) and best spectacle-corrected visual acuity improved significantly from 0.42 preoperatively to 0.29 postoperatively (P < 0.01) and 0.11 to 0.06 postoperatively (P < 0.01), respectively. The refractive cylinder reduced significantly from -3.07D to -2.63D (P < 0.05). The mean Km improved from 46.15D to 45.44D (P < 0.01) and mean Kmax from 54.03D to 52.52D (P < 0.01). 77% of eyes (n = 61) exhibited Kmax improvement postoperatively, and 56% showed an improvement in UDVA (n = 44). 16% (n = 13) had worsening of vision, but of these, only 1 patient had visual loss of more than 2 lines. No eyes had corneal haze reported at the final follow-up, and none required additional treatment. CONCLUSIONS: This standardized simultaneous t-PTK and CXL protocol is safe and effective for the treatment of progressive keratoconus, providing visual, refractive, and topographic improvements.

A Novel Role for Corneal Pachymetry in Planning Cataract Surgery by Determining Changes in Spherical Equivalent Resulting from a Previous LASIK Treatment.

Objectives: To provide a metric to differentiate between hyperopic and myopic ablation of a prior LASIK treatment based on the corneal pachymetry profile after laser vision correction (LVC). Methods: Pachymetry data were retrospectively recovered from patients who had previous LASIK for refractive purposes between 2019 and 2020. Patients with any corneal disorder were excluded. Ablation spherical equivalent was predicted from the central to semiperipheral corneal thickness (CPT) ratio, both values were provided by using the Pentacam user interface software (UI), and values were computed from extracted raw pachymetry data. Results: Data of 157 eyes of 81 patients were collected, of which data were analysed for 73 eyes of 73 patients to avoid concurrence of measurements in both eyes per subject (42% female; mean age 40.9; SD 12.8). The CPT ratio cutoff for distinction between myopic and hyperopic LASIK was 0.86 for Pentacam UI data. Sensitivity and specificity were 0.7 and 0.95, respectively. Accuracy increased with computation of the CPT ratio based on extracted raw data with sensitivity and specificity of 0.87 and 0.99, respectively. There was a marked linear correlation between the CPT ratio and the ablation spherical equivalent (R2 = 0.93). Conclusions: CPT ratio cutoffs can correctly classify if a cornea previously had a hyperopic versus myopic LASIK surgery and estimate the ablation spherical equivalent of such treatment. This could prove useful for increased accuracy of intraocular lens (IOL) calculations for patients with no historical data of their prior LVC surgery at the time of cataract surgery planning.

SCLERAL FIXATION OF CARLEVALE INTRAOCULAR LENS: A Systematic Review and Meta-Analysis.

PURPOSE: The mean change in best-corrected visual acuity (BCVA), intraocular pressure, and endothelial cell counts after intraocular lens (IOL) implantation and the incidence rate of postoperative complications were estimated by systematic review and meta-analysis to assess the surgical and refractive outcomes of the sutureless scleral fixation Carlevale IOL. METHODS: A literature search was conducted using PubMed, Embase, and Scopus. The weighted mean difference (WMD) was used to present the mean change in BCVA, intraocular pressure, and endothelial cell count after IOL implantation, whereas a proportional meta-analysis was used to estimate the pooled incidence rate of postoperative complications. RESULTS: In the meta-analysis of 13 studies involving 550 eyes, the pooled WMD of the mean change in BCVA showed a significant improvement in BCVA in patients who underwent Carlevale IOL implantation (WMD = 0.38, 95% confidence interval: 0.30-0.46, P < 0.001; heterogeneity [I 2 ] = 52.02%). The subgroup analyses indicated that the mean change in BCVA was not significantly higher according to the last follow-up visit, with no statistically significant subgroup effect ( P = 0.21) (WMD up to 6 months: 0.34, 95% confidence interval: 0.23-0.45, I 2 = 58.32%, WMD up to 24 months: 0.42, 95% confidence interval: 0.34-0.51, I 2 = 38.08%). In the meta-analysis of 16 studies involving 608 eyes, the pooled incidence rate of postoperative complications was equal to 0.22 (95% confidence interval: 0.13-0.32, I 2 = 84.87, P ≤ 0.001). CONCLUSION: Carlevale IOL implantation represents a reliable method of restoring vision in eyes with missing capsular or zonular support.

Recommendation for Presbyopia-Correcting Intraocular Lenses: A Delphi Consensus Statement by the ESASO Study Group.

PURPOSE: To establish consensus among experts in lens and refractive surgery to guide general ophthalmologists on issues related to presbyopia-correcting intraocular lenses (IOLs). DESIGN: A modified Delphi method to reach a consensus among experts. METHODS: A steering committee formulated 105 relevant items grouped into four sections (preoperative considerations, IOL selection, intraoperative considerations, and postoperative considerations). The consensus was defined as ≥ 70% of experts agreeing with the evaluation of a statement. RESULTS: Ten experts participated and completed all rounds of questionnaires (100% response rate). Of 68 items considered in the preoperative considerations, consensus was achieved in 48 (70.6%). There was a lack of consensus over IOL selection, the experts only agreed on the importance of the patient's habits for the optical IOL design selection. Of the 14 considerations related to intraoperative issues, the experts reached a consensus on 10 (71.4%). The postoperative considerations section reached the highest consensus in 10 items of 13 (76.9%). CONCLUSIONS: Key recommendations for a diffractive multifocal IOL were a potential postoperative visual acuity > 0.5, a keratometry between 40-45 diopters, a pupil >2.8 mm under photopic conditions and <6.0 mm under scotopic conditions, a root mean square of higher order corneal aberrations <0.5 µm for 6-mm pupil size, while monofocal or non-diffractive IOLs should be considered for patients with coexisting eye disorders. A lack of agreement was found in the issues related to the IOL selection.

Corneal Collagen Cross-Linking for Late Onset Progressive Keratoconus in Iridocorneal Endothelial Syndrome.

PURPOSE: The aim of this study was to report the first case of successful use of corneal collagen cross-linking (CXL) to halt the progression of keratoconus in a patient with concurrent iridocorneal endothelial (ICE) syndrome. METHODS: A 30-year-old White man was referred to our subspecialty corneal clinic for further investigation of right corectopia. The patient was asymptomatic and was otherwise fit. Slit-lamp examination revealed a right oval-shaped pupil decentered superiorly, a transillumination defect at the 5-o'clock position, minimal gutta-like changes in the corneal endothelium, and few inferior peripheral anterior synechiae. Dilated fundoscopy was normal in both eyes, with healthy optic discs, maculae, and peripheral retinae. Specular microscopy and slit-lamp findings suggested ICE syndrome. Subsequent investigation with corneal tomography showed progressive signs of inferior corneal ectasia with steepening, and thinning in the right eye, consistent with keratoconus. The left eye was unremarkable. RESULTS: Epithelium-off accelerated corneal CXL was performed in the affected eye. Early post-CXL follow-up (1 week) was unremarkable, and further follow-ups were arranged at 3, 6, 12, and 24 months, respectively. In subsequent reviews, the patient's vision and corneal tomography findings were stable. CONCLUSIONS: We describe the first case of corneal CXL for progressive keratoconus with ICE syndrome. co-existing keratoconus and ICE syndrome can occur, and corneal cross-linking was used successfully in this case to halt keratoconus progression. However, further studies will need to establish the impact of epithelium-off corneal cross-linking, especially in more severely affected eyes.

Phakic intraocular lens implantation in a case of Tourette syndrome exacerbated by wearing glasses and contact lenses.

A 25-year-old longsighted woman presented with a history of spectacle and contact lens induced exacerbation of Tourette syndrome symptoms. Preoperatively, she had very poor unaided vision (6/60), achieving good (6/9) vision in both eyes with spectacle correction. The patient underwent bilateral simultaneous implantation of phakic implantable collamer lens (ICL) implants (STAAR, USA) which sit in front of the natural lens. Postoperatively, her uncorrected visual acuity was markedly improved as were her manifestations of Tourette syndrome. She achieved her full potential of unaided vision (6/9). This is the first documented case of Tourette syndrome triggered by glasses and contact lenses in which bilateral phakic toric lens implants were effective in improving vision and controlling motor symptoms. Phakic toric ICL implantation is a reversible technique for the correction of visually significant ametropia in selected patients and has improved this patient's quality of life.

Severe corneal melting after cataract surgery in patients prescribed topical postoperative NSAIDs and dexamethasone/neomycin combination therapy.

Three patients using a postoperative combination of topical ketorolac (Acular) and neomycin/polymyxin B sulfate/dexamethasone (Maxitrol) were diagnosed with atypical keratopathy soon after routine cataract surgery. An immediate retrospective analysis of hospital patients who had used this topical drug combination in the previous year identified 10 other patients who also had significant corneal pathology after uneventful cataract surgery. Five of the 13 affected patients had corneal melting and 1 patient had corneal perforation and endophthalmitis. At the last recorded follow-up appointment, 8 of the 13 patients had a visual acuity of 6/36 or worse. Corneal melting is a rare complication of topical nonsteroidal anti-inflammatory drugs (NSAIDs). We propose that the combined use of topical NSAIDs and other agents, such as neomycin and benzalkonium, that further compromise the corneal epithelium, should be used with vigilance and increased awareness of potential keratopathy and permanent visual morbidity.

Corneal and Scleral Problems Caused by Skin-Lightening Creams.

PURPOSE: To present a case series of patients with corneal and scleral changes associated with the use of skin-lightening creams. This is the first report of corneal changes with these widely available creams. METHODS: Three patients of West African origin presented with strikingly similar skin, corneal, and scleral changes and were found to have all been using skin-lightening creams containing hydroquinone. Histopathology was obtained for 1 patient. RESULTS: Three patients were referred to the corneal clinics of 2 hospitals with corneal changes and a history of blurred vision for 1 to 3 years. There was a 60-year-old woman from Nigeria and a 68-year-old woman and a 73-year-old man both from Ghana. All 3 had been using skin-lightening lotions containing hydroquinone on their faces for between 3 and 15 years and had black-blue facial pigmentation of exogenous ochronosis, a recognized complication of these creams. Their corneas all had horizontal striae radiating across the posterior corneas with scleral thinning and plaques. Linear brown epithelial pigmentation was observed within the lower third of the corneas. Biopsy of the sclera in 1 patient showed ochronosis. CONCLUSIONS: We present previously unreported eye changes associated with the use of skin-lightening creams containing hydroquinone, with a triad of signs: posterior corneal striae radiating from 3 o'clock to 9 o'clock, thinning and plaques in the sclera, and a normal endothelial cell count. Similar pathological changes are seen in exogenous ochronosis, a recognized skin complication of hydroquinone, are seen in the sclera.

Cytomegalovirus infection is not a major cause of corneal graft failure in the United Kingdom.

BACKGROUND: Cytomegalovirus (CMV) endotheliitis is a significant cause for acute corneal allograft rejection in East Asian populations, where there is a high CMV seroprevalence. To determine how frequently CMV is associated with corneal graft failure in the UK, we looked for the presence of CMV DNA in grafts that had failed and had been removed at repeat keratoplasty. We also looked for CMV DNA in corneal rims discarded after corneal transplantation. METHODS: In this retrospective study, we identified 54 cases of corneal graft failure following endothelial rejection and 38 control grafts that had failed without a history of endothelial rejection. For these groups archived formalin-fixed paraffin-embedded (FFPE) tissue samples were retrieved. We also prospectively examined 80 non-fixed cornea rims following transplantation surgery. In all samples nested quantitative PCR was used to identify CMV, herpes simplex virus (HSV) and varicella zoster virus (VZV) DNA. We also used in situ hybridisation to examine for CMV DNA in the FFPE samples. RESULTS: No CMV or VZV DNA was detected in any of the archived case or control FFPE tissues. One corneal rim from the control group was positive for HSV. In situ hybridisation for CMV was negative for CMV in all FFPE samples. No CMV, VZV or HSV DNA was detected in the donor corneal rim samples. CONCLUSION: CMV DNA was not identified in excised failed corneal tissue or from tissue prior to transplantation. We infer that CMV infection is not a significant factor risk for corneal graft failure in the United Kingdom.

Intraoperative anterior segment optical coherence tomography: a novel assessment tool during deep anterior lamellar keratoplasty.

PURPOSE: To describe the use of high-resolution anterior segment optical coherence tomography (AS-OCT) during deep anterior lamellar keratoplasty (DALK). DESIGN: Prospective case series. METHODS: At the Singapore National Eye Centre we performed sequential intraoperative AS-OCT scans using iVue 100-2 (Optovue, Fremont, CA, USA) during various DALK techniques. RESULTS: In case 1 (corneal scarring) the OCT images helped to guide manual dissection, showed the depth of the needle track before air injection, and identified the location of a small bubble when the big bubble failed. In cases 2 (macular dystrophy) and 3 (lattice), viscodissection was undertaken, but in case 2 the OCT showed the viscoelastic trapped intrastromally, compared to case 3, in which the viscobubble dissection was successful. In case 4 (irregular corneal thinning and scarring), AS-OCT enabled accurate decision on initial trephination and guided dissection. In case 5 (keratoconus), the OCT showed the achieved big-bubble and detached Descemet membrane. Case 6 was a repeat DALK; the OCT guided the manual dissection of the residual stroma underlying the failed graft. In case 7, the OCT showed an intrastromal retention of fluid that was not detectable by the operating microscope due to diffuse scarring following alkaline injury. The OCT helped to assess the location of the Descemet membrane and guided the manual dissection. CONCLUSIONS: Intraoperative high-definition AS-OCT obtained good-quality images of the cornea during DALK and proved useful in various cases of DALK to help the surgeon decide on a number of surgical steps.

Reversible femtosecond laser-assisted myopia correction: a non-human primate study of lenticule re-implantation after refractive lenticule extraction.

LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.

Ex-vivo ocular surface stem cell therapies: current techniques, applications, hurdles and future directions.

Engineered tissue derived from ocular surface stem cells (SCs) are a cutting edge biotechnology for repair and restoration of severely damaged eyes as a result of ocular surface dysfunction because of SC failure. Ex-vivo SC expansion techniques have advanced significantly since the first patients were treated in the late 1990s. The techniques and clinical reports reviewed here highlight the evolution and successes of these techniques, while also revealing gaps in our understanding of ocular surface and SC biology that drives further research and development in this field. Although hurdles still remain before stem-cell-based therapies are more widely available for patients with devastating ocular surface disease, recent discoveries in the field of mesenchymal SCs and the potential of induced pluripotent SCs heralds a promising future for clinicians and our patients.

Reproducibility and age-related changes of ocular parametric measurements in rabbits.

BACKGROUND: The rabbit is a common animal model for ophthalmic research, especially corneal research. Ocular structures grow rapidly during the early stages of life. It is unclear when the rabbit cornea becomes mature and stabilized. We investigated the changes of keratometry, refractive state and central corneal thickness (CCT) with age. In addition, we studied the intra- and inter-observer reproducibility of anterior chamber depth (ACD) and anterior chamber width (ACW) measurements in rabbits using anterior segment-optical coherence tomography (AS-OCT). RESULTS: The growth of New Zealand White rabbits (n = 16) were monitored from age 1 to 12 months old. Corneal keratometric and refractive values were obtained using an autorefractor/keratometer, and CCT was measured using an AS-OCT. Keratometry and CCT changed rapidly from 1 to 7 months and appeared to be stabilizing after 8 months. The reduction of corneal curvature was approximately 1.36 diopter (D)/month from age 1 to 7 months, but the change decelerated to 0.30 D/month from age 8 to 12 months. An increase of 10 µm/month in CCT was observed from age 1 to 7 months, but the gain was reduced to less than 1 µm/month from age 8 to 12 months. There was a hyperopic shift over the span of 12 months, albeit the increase in spherical equivalent was slow and gradual. Rabbits of random age were then selected for 2 repeated ACD and ACW measurements by 2 independent and masked observers. Bland-Altman plots revealed a good agreement of ACD and ACW measurements inter- and intra-observer and the ranges of 95% limit of agreement were acceptable from a clinical perspective. CONCLUSIONS: Corneal keratometry, spherical equivalent refraction and CCT changed significantly during the first few months of life of rabbits. Young rabbits have been used in a large number of eye research studies. In certain settings, the ocular parametric changes are an important aspect to note as they may alter the findings made in a rabbit experimental model. In this study, we have also demonstrated for the first time a good between observer reproducibility of measurements of ocular parameters in an animal model by using an AS-OCT.

Effect of different femtosecond laser-firing patterns on collagen disruption during refractive lenticule extraction.

PURPOSE: To evaluate the changes in corneal collagen architecture subjected to different laser-firing patterns during refractive lenticule extraction. SETTING: Singapore Eye Research Institute, Singapore. DESIGN: Experimental study. METHODS: Refractive lenticule extraction was performed in rabbits without lenticule removal. Rabbits were divided into 4 groups that had incisions in the following firing patterns: (A) from periphery in (lenticule's posterior surface) and from center out (lenticule's anterior surface); (B) from center out and from center out; (C) from periphery in and from periphery in; and (D) from center out and from periphery in. The corneas were collected 18 hours postoperatively and were subjected to immunofluorescent staining of fibronectin, CD11b, and collagen type I. Ultrastructural analysis was performed using transmission electron microscopy (TEM). RESULTS: Refractive lenticule extraction-treated corneas showed no significant difference in fibronectin and CD11b expression. Similar expression patterns of collagen type I were observed in corneas that had femtosecond firing patterns A, B, and C; however, a discontinuous and relatively more intense staining pattern along the anterior plane of the lenticule was detected in corneas treated with pattern D. The TEM also showed a more disrupted collagen arrangement along the anterior incision site in pattern D-treated corneas. CONCLUSIONS: Differential laser firing patterns during refractive lenticule extraction resulted in different levels of collagen derangement along the anterior plane of the lenticule, with pattern D showing the most disrupted surface. Such disruption in the collagen architecture might affect postoperative visual recovery and refractive outcomes. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.