Evaluating the efficacy of Rho kinase inhibitor eye drops in the management of corneal edema: A single-center retrospective cohort study.

PURPOSE: This study aimed to evaluate the efficacy of ripasudil in managing various corneal edema conditions. MATERIALS AND METHODS: This single-center retrospective analysis was conducted at Hadassah Medical Center and involved 16 patients with 17 eyes. Patients were selected based on diagnostic criteria, primarily corneal edema. The conditions were as follows, listed by frequency: postcataract surgery (31.25%), postpenetrating keratoplasty (25%), post-Descemet's membrane endothelial keratoplasty (18.75%), Fuchs' endothelial corneal dystrophy (12.5%), status post-Ahmed glaucoma valve (6.25%), and status posttrabeculectomy (6.25%). The treatment regimen involved topical administration of ripasudil hydrochloride hydrate (Glanatec® 0.4%), administered three times a day or tailored to condition severity. Efficacy was assessed using pre- and posttreatment measurements of best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC), along with slit-lamp and optical coherence tomography examinations. RESULTS: The average duration of ripasudil treatment was approximately 4.9 ± 2.2 months. Significant improvements were observed in BCVA, changing from a pretreatment value of 1.106 ± 0.817 logMAR to a posttreatment value of 0.56 ± 0.57 logMAR (P = 0.0308). CCT also showed a significant reduction, from 619.50 ± 56.36 µm pretreatment to 572.5 ± 75.48 µm posttreatment (P = 0.0479). ECC showed a marginal but not statistically significant increase, from 849.00 ± 570.72 cells/mm² pretreatment to 874.75 ± 625.59 cells/mm² posttreatment (P = 0.9010). CONCLUSION: The study provides robust evidence supporting the use of ripasudil in managing corneal edema. Significant improvements in key ocular metrics such as BCVA and CCT were observed, enhancing the overall quality of life for patients suffering from various forms of corneal edema.

Neurotrophic keratitis: inflammatory pathogenesis and novel therapies.

PURPOSE OF REVIEW: Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management. RECENT FINDINGS: Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging. SUMMARY: Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.

Metagenomic sequencing for investigation of a national keratoconjunctivitis outbreak, Israel, 2022.

BackgroundEpidemics of keratoconjunctivitis may involve various aetiological agents. Microsporidia are an uncommon difficult-to-diagnose cause of such outbreaks.AimDuring the third quarter of 2022, a keratoconjunctivitis outbreak was reported across Israel, related to common water exposure to the Sea of Galilee. We report a comprehensive diagnostic approach that identified Vittaforma corneae as the aetiology, serving as proof of concept for using real-time metagenomics for outbreak investigation.MethodsCorneal scraping samples from a clinical case were subjected to standard microbiological testing. Samples were tested by calcofluor white staining and metagenomic short-read sequencing. We analysed the metagenome for taxonomical assignment and isolation of metagenome-assembled genome (MAG). Targets for a novel PCR were identified, and the assay was applied to clinical and environmental samples and confirmed by long-read metagenomic sequencing.ResultsFluorescent microscopy was suggestive of microsporidiosis. The most abundant species (96.5%) on metagenomics analysis was V. corneae. Annotation of the MAG confirmed the species assignment. A unique PCR target in the microsporidian rRNA gene was identified and validated against the clinical sample. The assay and metagenomic sequencing confirmed V. corneae in an environmental sludge sample collected at the exposure site.ConclusionsThe real-time utilisation of metagenomics allowed species detection and development of diagnostic tools, which aided in outbreak source tracking and can be applied for future cases. Metagenomics allows a fully culture-independent investigation and is an important modality for public health microbiology.

Ocular surface inflammation and ectatic corneal disorders.

PURPOSE OF REVIEW: Inflammatory mediators are a focus of recent corneal ectasia (CE) research and are a profound, modifiable contributor to CE in general and keratoconus (KC) in particular, opening a path to explore new methods of control. As advanced imaging technology and expanded population screening allow for earlier detection, the possibility of early intervention can profoundly change the prognosis of CE. RECENT FINDINGS: Significant increases in the inflammatory mediators and immune components have been observed in the cornea, tear fluid, and blood of ectasia patients, while inflammation dampeners such as vitamin D and their receptors are reduced. Atopy and allergy have a strong association with KC, known to increase itch factors and stimulate eye rubbing, a risk factor in ectasia pathogenesis. Management of atopy or allergic conditions and topical anti-inflammatories has helped stabilize CE disease. SUMMARY: Strategies such as monitoring inflammatory factors and using immune or inflammatory modulators, including managing subclinical inflammation, may be clinically beneficial in stabilizing the disease and improving outcomes. The detected factors are biomarkers, but as yet unproven to be sensitive or specific enough to be considered biomarkers for early detection of CE. The establishment of such biomarkers could improve the therapeutic outcome.

Outcome indicators for cross linking in pediatric keratoconus.

Purpose: To evaluate the predictive factors for successful corneal collagen cross-linking (CXL) in pediatric patients with Keratoconus (KC). Methods: This retrospective study was conducted using a prospectively built database. Patients (18 years old or younger) underwent CXL for KC between 2007 and 2017, with a 1-year follow-up period or longer. The outcomes included changes in Kmax (delta [Δ] Kmax = Kmaxlast - Kmaxpre) and LogMAR visual acuity (ΔLogMAR = LogMARlast - LogMARpre).The effects of CXL type (accelerated or non-accelerated), demographics (age, sex, background of ocular allergy, ethnicity), preoperative LogMAR visual acuity, maximal corneal power (Kmax), pachymetry (CCTpre), refractive cylinder, and follow-up (FU) time on the outcomes were analyzed. Results: One hundred thirty-one eyes of 110 children were included (mean age, 16 ± 2 years; range, 10-18 years). Kmax and LogMAR improved from baseline to last visit: from 53.81 D ± 6.39 D to 52.31 D ± 6.06 D (p < 0.001) and from 0.27 ± 0.23 LogMAR units to 0.23 ± 0.19 LogMAR units (p = 0.005), respectively. A negative ΔKmax (meaning corneal flattening) was associated with a long FU, low CCTpre, high Kmaxpre, high LogMARpre, and non-accelerated CXL on univariate analysis. High Kmaxpre and non-accelerated CXL were associated with negative ΔKmax in the multivariate analysis.A negative ΔLogMAR (meaning vision improvement) was associated with a high LogMARpre in univariate analysis. Conclusion: CXL is an effective treatment option in pediatric patients with KC. Our results showed that the non-accelerated treatment was more effective than the accelerated treatment. Corneas with advanced disease had a greater effect on CXL.

Differences in retinal images quality between normal and subclinical keratoconus and its association to posterior corneal asymmetry.

PURPOSE: To compare retinal image quality in subclinical keratoconus and normal eyes using a double-pass aberrometer and to correlate it with posterior surface deformation. METHODS: Sixty normal corneas were compared to 20 subclinical keratoconus (SKC) corneas. Retinal image quality was assessed using a double-pass system in all the eyes. The objective scatter index (OSI) modulation transfer function (MTF) cutoff, Strehl ratio (SR), and Predicted Visual Acuity (PVA) values at 100%, 20%, and 9% were calculated and compared between the groups. Posterior corneal asymmetry was measured using a combined Placido Dual Scheimpflug Analyzer, and correlations were tested with all optical quality parameters. RESULTS: Significant decrease in optical quality parameters was observed in SKC eyes compared with that in normal eyes. Subclinical KC eyes expressed greater scattering (OSI = 0.66 ± 0.36 vs 0.47 ± 0.26) and reduced contrast images (MTF and SR) than normal eyes, with 38.82 ± 9.4 and 0.22 ± 0.04, and 44.35 ± 7.1 and 0.24 ± 0.04, respectively. The reduction in the image contrast parameters (MTF and SR) was strongly correlated to the level of posterior corneal asymmetry in SKC. The greater the posterior asymmetry, the more affected was the image contrast, with r = -0.63 and -0.59, respectively for MTF and SR. CONCLUSION: Retinal image quality was significantly more affected in eyes with subclinical keratoconus than in normal eyes. The reduction in optical quality observed in subclinical keratoconus was strongly associated with the increased asymmetry of the posterior cornea.

Early Impact of Laser Vision Correction (LVC) on the Stability and Quality of the Retinal Image.

This retrospective comparative study analyzes the early postoperative impact of laser vision correction for myopia on the optical quality and stability of functional vision using a double-pass aberrometer. Retinal image quality and visual function stability were assessed preoperatively, one and three months after myopic laser in situ keratomileuses (LASIK) and photorefractive keratectomy (PRK) using double-pass aberrometry (HD Analyzer, Visiometrics S.L, Terrassa, Spain). The parameters analyzed included vision break-up time (VBUT), objective scattering index (OSI), modulation transfer function (MTF), and Strehl ratio (SR). The study included 141 eyes of 141 patients, of whom 89 underwent PRK and 52 underwent LASIK. No statistically significant differences were noted between the two techniques in any analyzed parameters at three months postoperatively. However, a significant drop was observed in all parameters one month after PRK. Only the OSI and VBUT remained significantly altered from baseline at the three months follow-up visit, with an increased OSI by 0.14 +/- 0.36 (p < 0.01) and a shortened VBUT by 0.57 +/- 2.3 s (p < 0.01). No correlation was found between the changes in optical and visual quality parameters and age, ablation depth, or postoperative spherical equivalent. The stability and quality of the retinal images were similar between LASIK and PRK at three months postoperatively. However, significant degradation in all parameters was found one month after PRK.

Corneal complications of rheumatoid arthritis.

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the joints. Extra-articular manifestations (EAMs) are common and may affect up to 40.6% of patients. Ocular EAM can occur in 39% of the patients. The cornea is involved by different pathogenic mechanisms and corneal disease varies from mild symptoms to severe corneal ulceration and melting with visual loss. Severe corneal involvement is associated with increased mortality in RA patients. We aimed to review the prevalence, mechanisms, management and overall impact of corneal involvement in RA patients. RECENT FINDINGS: Corneal involvement is frequent among RA patients. With the wider use of systemic immunosuppression, in particular the disease-modifying antirheumatic drugs (DMARDs), and with improvement of surgical techniques, spontaneous and surgery-related corneal ulceration and melting is becoming less common. However, RA patients are still at risk and should be carefully managed. SUMMARY: RA-related corneal complications are associated with a decreased quality of life and poor ocular and systemic prognosis. Prompt recognition and a multidisciplinary approach involving topical ophthalmic management and systemic immunosuppression are the key factors to maintain ocular integrity and avoid a lethal outcome.

Predicting factors for the efficacy of cross-linking for keratoconus.

PURPOSE: To evaluate predictors for success in corneal crosslinking (CXL) for keratoconus in a large cohort and extended follow-up. DESIGN: A retrospective study based on a prospectively built database. METHODS: Participants underwent CXL for keratoconus from 2007 to 2018. Statistical analysis was performed for patients with at least 1-year follow-up. We analyzed effects of CXL type (Epithelium-on or Epithelium-off and Accelerated (9mW/cm2@10min) or Standard (3mW/cm2@30min)) and pre-operative factors including age, gender, baseline LogMAR visual acuity (LogMARpre), maximal corneal power (Kmaxpre), pachymetry, refractive and topographic cylinders, spherical equivalent (SEpre), mean corneal power (MeanK) and follow-up time on outcome measures. The outcome measures were the final change of Kmax (Delta Kmax) and the final change in LogMAR visual acuity (Delta LogMAR). A more negative Delta Kmax or Delta LogMAR represents a favorable effect of crosslinking. RESULTS: 517 eyes had Kmax results, and 385 eyes had LogMAR results with more than one year follow-up. These eyes were included in the study. The mean follow-up time was 2.29 years. Mean Kmax decreased from 54.07±5.99 diopters to 52.84±5.66 diopters (p<0.001), and Mean LogMAR decreased from 0.28±0.20 to 0.25±0.21 (p<0.001). Non-accelerated epithelium-off CXL resulted in greater flattening of Kmax when compared with other protocols. Visual acuity improvement was similar when comparing different CXL protocols. Multivariate analysis showed four factors associated with negative Delta Kmax: high Kmaxpre, high SEpre, high MeanKpre, and non-accelerated procedure. Multivariate analysis showed three factors associated with negative Delta LogMAR: high LogMARpre, high SEpre, and Low MeanKpre. After excluding corneas with Kmaxpre >65 D or Pachymetry<400 microns, multivariate analysis showed that high Kmaxpre, high SEpre, and non-accelerated CXL were associated with negative Delta Kmax while high LogMARpre and high SEpre were associated with negative Delta LogMAR. CONCLUSION: CXL for keratoconus is a highly effective treatment, as evident by its effects on the outcome measures: Delta Kmax and Delta LogMAR. CXL was more successful in eyes with high Kmaxpre, high SEpre, and high LogMARpre, which express disease severity. The non-accelerated epithelium-off protocol was associated with greater flattening of corneal curvature but did not show a better effect on visual acuity as compared to the other CXL protocols.

Vernal keratoconjunctivitis and keratoconus.

PURPOSE OF REVIEW: Vernal keratoconjunctivitis (VKC) is a severe allergic inflammatory disease affecting the conjunctiva in children and young adults. Keratoconus (KC) is a progressive corneal disease characterized by thinning of the corneal stroma, increased and asymmetric corneal curvature, with a potential for significant visual deterioration and is one of the most common corneal complications of VKC. We aimed to review the association of these two diseases, with focus on the mechanisms, prevalence, natural history and treatment strategies of KC associated with VKC. RECENT FINDINGS: KC is a common complication of VKC. KC prevalence can be as high as 26.8% among VKC patients, whereas abnormal corneal topography may appear in up to 71% of them. It is more severe and progresses faster in the setting of VKC (P < 0.05), with remarkable visual deterioration and with an increased need for keratoplasty. Crosslinking treatment and corneal transplantation appear to be as effective for KC patients with VKC as compared to the patients without VKC. However, postoperative complications are higher in patients with VKC and demand close monitoring, tight control of local inflammation and prompt awareness with consequent restrain of eye rubbing. SUMMARY: Patients with VKC should be closely monitored for KC. Prompt recognition of VKC and KC allows tight control of KC pathogenesis mechanisms, timely management of KC progression and preservation of vision and quality of life of young patients.

Keratoplasty for Keratoconus in Young Patients: Demographics, Clinical Features, and Post-transplant Outcomes.

PURPOSE: To examine pretransplant findings and outcomes of corneal transplants for keratoconus in children. DESIGN: Retrospective cohort (national registry) study. METHODS: Data on all patients aged 16 or younger (n = 170) who had a first transplant for keratoconus between 2003 and 2018 in all corneal transplant centers in the UK were compared to adult patients aged 17 and older (n = 7,191). The influence of demographic variables, pretransplant corneal findings, and transplant type on 2-year visual, rejection-free, and transplant survival outcomes was examined. RESULTS: Children had poorer pretransplant visual acuity and higher rates of corneal vascularization and ocular surface disease than adults. However, 2-year post-transplant corrected visual acuity reached 20/20 or better in 35% of children compared to 28% of adults (P = .1). Transplant rejection and failure rates were 11% (P = .79) and 3% (P = .31), respectively, for children, which were comparable to rates for adults. Endothelial rejection was reported following penetrating keratoplasty (PK) in 13% of children (10% in adults). Irreversible rejection was not recorded for any transplant in a child. Despite a lack of difference in transplant outcomes, there was a significant age effect in the Cox regression model for transplant rejection, such that for every 5-year increase in age there was a 6% reduction in the hazard of rejection. Transplant survival following anterior lamellar keratoplasty and PK in children was similar. CONCLUSIONS: Young keratoconus patients have excellent transplant outcomes and visual results comparable to adults. Overall, the hazard of rejection was found to decrease with advancing age. However, in this large cohort of young patients with keratoconus and poor vision, there is no evidence of outcome advantage in delaying transplant until adult years.

Predictive factors for efficacy and safety in refractive surgery for myopia.

PURPOSE: To evaluate the predictive factors for safety and efficacy in laser refractive surgery for myopia. SETTING: A singular refractive surgery center, at a University-affiliated tertiary medical center. DESIGN: Retrospective cohort study. METHODS: Study population-A total 8,775 eyes having laser refractive laser procedures for myopia (in4,623 patients). Observation procedures-Using a prospective database of refractive procedures performed over the span of 13 years, variables such as gender, age, type of surgery, date of surgery, pre-operative corneal thickness and Spherical Equivalent (SEQ) were evaluated. Main outcome measures-Proportion of patients with Safety index higher than 0.85 and Efficacy index higher than 0.80. RESULTS: 91.9% and 86.0% of all evaluated eyes were above the safety and efficacy cut-off levels, respectively. Younger age was significantly correlated with safety and efficacy indices above the cut-off levels (p<0.001). Male gender was significantly correlated with efficacy above the cut-off level (p<0.001). Myopic eyes with lower SEQ were associated with both safety (p = 0.002) and efficacy (p<0.001) indices above the cut-offs. The surgical procedure was found to significantly affect the outcome only using univariate analysis: Safety was higher in Photorefractive Keratectomy (PRK), while Efficacy was higher in Laser Assisted In Situ Keratomileusis (LASIK) (p<0.001, respectively) but no difference was found using multivariate analysis. Safety index above the cut-off level increased over the years (p<0.001). CONCLUSIONS: Efficacy in refractive surgery for myopia is correlated with younger age, male gender and low myopia. Safety is correlated with younger age, low myopia and increases over the years. Multivariate analysis found no differences between PRK and LASIK regarding safety and efficacy.

Trends of Bacterial Keratitis Culture Isolates in Jerusalem; a 13- Years Analysis.

PURPOSE: To describe the trends in pathogens and antibacterial resistance of corneal culture isolates in infectious keratitis during a period of 13 years at Hadassah-Hebrew University Medical Center. METHODS: A Retrospective analysis of bacterial corneal isolates was performed during the months of January 2002 to December 2014 at Hadassah Hebrew University Medical Center. Demographics, microbiological data and antibiotic resistance and sensitivity were collected. RESULTS: A total of 943 corneal isolates were analyzed during a 13 year period. A total of 415 positive bacterial cultures and 37 positive fungal cultures were recovered, representing 48% of the total cultures. The Annual incidence was 34.78 ± 6.54 cases. The most common isolate was coagulase-negative staphylococcus (32%), which had a significant decrease in trend throughout the study period (APC = -8.1, p = 0.002). Methicillin-resistant Staphylococcus aureus (MRSA) appears to have a decrease trend (APC = -31.2, P = 0.5). There was an increase in the resistance trend of coagulase-negative staphylococci to penicillin (APC = 5.0, P = <0.001). None of the pathogens had developed any resistance to Vancomycin. (P = 0.88). CONCLUSIONS: Coagulase negative staphylococci were the predominant bacteria isolated from patients with keratitis. There was no significant change in the annual incidence of cases of bacterial keratitis seen over the past 13 years. Keratitis caused by MRSA appeared to decrease in contrast to the reported literature.

Silicone hydrogel mini-scleral contact lenses in early stage after corneal collagen cross-linking for keratoconus: a retrospective case series.

BACKGROUND: The aim was to the evaluate performance of a novel silicone hydrogel mini-scleral contact lens (SHmS) for optical correction of keratoconus in the early stages after the corneal collagen cross-linking procedure (CXL). METHODS: We retrospectively analysed the visual acuity improvement and corneal adaptation in the first 10 eyes of nine patients fitted with SHmS lenses one to 3.5 months after corneal collagen cross-linking. The lenses were designed to rest over the patients' sclera and peri-limbal cornea and vault the central cornea with minimal support over it. Visual acuities with manifest refraction and contact lenses, refractive and topographical values (Kmin and Kmax) were evaluated on lens dispensing and after six month of lens wearing. Ocular physiological responses were evaluated using the Institute of Eye Research (IER) grading scales. RESULTS: SHmS fitting was performed 2.1 ± 0.97 (SD) months after collagen cross-linking. Mean follow up was 10.9 ± 4.41 months (range six to 18 months). Mean decimal visual acuity with SHmS was 0.66 ± 0.22 (approximately 6/9 Snellen fraction, range 0.3 to 0.1) or 0.75 ± 0.14 (approximately 6/8.1, range 0.5 to 1.0), when omitting two amblyopic eyes. Nine (90 per cent) eyes were successfully fitted, that is, able to wear the lenses for 10 hours per day or longer. Mean wearing time was 11.7 hours (range six to 14) per day. No corneal neovascularisation or papillary reaction was found in all fitted eyes. CONCLUSIONS: SHmS contact lenses provide successful visual rehabilitation shortly after corneal collagen cross-linking. This new soft contact lens design with scleral fixation and minimal apical touch was demonstrated to be safe shortly after collagen cross-linking, as the avoidance of contact with the treated zone minimises contact lens influence on corneal recovery.