The Utilization of Brillouin Microscopy in Corneal Diagnostics: A Systematic Review.

Corneal biomechanical data has been used since 2005 to screen for keratoconus and corneal ectasia by corneal specialists. Older technology uses force applanation techniques over a 3 mm area in the central cornea, making it highly dependent on extraneous variables and unable to calculate the elasticity of the tissue. Brillouin microscopy is a newer method that uses a natural shift in the frequency of light as it passes through a material. This frequency shift can be used to estimate the viscoelasticity of the tissue. The advantage of Brillouin microscopy is that it can create a full three-dimensional (3D) map of the entire cornea without direct contact. A literature search was conducted using the databases PubMed, Google Scholar, and Ovid regarding the applications of Brillouin microscopy in corneal diagnostics. A final total of 16 articles was included describing the various ex vivo and in vivo studies conducted using Brillouin microscopy. Applications of this technology spanned from keratoconus diagnosis to post-corneal refractive surgery evaluation. All studies evaluated corneal biomechanics and other corneal properties through the quantification of Brillouin frequency shifts. Many of the studies found that this diagnostic device is capable of detecting subtle changes in corneal thickness and biomechanics in keratoconic corneas at a high level of specificity and sensitivity. However, limitations of Brillouin microscopy may include the duration of time required for use and fluctuations in accuracy depending on the corneal hydration state. Future technology seems to be geared toward a combination of optical coherence tomography (OCT) and Brillouin microscopy, using OCT as a three-dimensional pupil-tracking modality. Further research and understanding of the technology involved will lead to better care of patients in the field of ophthalmology.

The impact of interrupted corneal collagen crosslinking (CXL) treatment.

PURPOSE: To evaluate progression of keratoconus in patients where CXL treatment was interrupted due to insufficient swelling of the cornea. METHODS: A retrospective review was conducted of all patients with keratoconus diagnosis who underwent CXL at the Department of Ophthalmology, Örebro University Hospital (USÖ) during the years 2010-2017. In total 377 eyes of 280 patients were screened for inclusion. In 17 eyes (15 patients), the treatment was interrupted due to insufficient swelling of the cornea. Patient journals were reviewed and keratometry examinations were analysed for long-term progression. RESULTS: Eleven eyes (nine patients) were included in the study. Five eyes showed no signs of progression after the interrupted CXL treatment. In one eye progression continued, however, first after a period of a number of years, indicating a delayed course of clinical progression. CONCLUSION: This study indicates that debridement of the corneal epithelium and riboflavin administration without intense UVA radiation may slow or arrest the progression of keratoconus, likely due to photosensitisation from ambient light.

Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

Immediate postoperative keratitis caused by Rhizopus species following standard CXL for keratoconus: A case report and literature review.

PURPOSE: To report the first case of Rhizopus sp keratitis in a 15-year-old male patient who had undergone a conventional Epi-off CXL procedure for progressive keratoconus. METHODS: A 15-year-old male studying at school presented with defective vision in both eyes recently. He was diagnosed with progressive keratoconus in the right eye more than left eye. After the conventional CXL procedure, the patient developed corneal ulcer on third postoperative day. RESULTS: The microbiological diagnosis of both BCL and ulcer revealed Rhizopus sp. The patient responded to topical antifungals, and the ulcer entirely healed with a large central scar. CONCLUSION: Rhizopus keratitis is rare in a healthy individual. Ours is the first case report of Rhizopus keratitis in patient undergone CXL.

UV light-mediated corneal crosslinking as (lymph)angioregressive pretreatment to promote graft survival after subsequent high-risk corneal transplantation (CrossCornealVision): protocol for a multicenter, randomized controlled trial.

BACKGROUND: Good vision highly depends on the transparency of the cornea, which is the "windscreen" of the eye. In fact, corneal blindness due to transparency loss is the second most common cause of blindness worldwide, and corneal transplantation is the main cure. Importantly, the cornea is normally avascular but can secondarily be invaded by pathological (blood and lymphatic) vessels due to severe inflammation, and the survival prognosis of a corneal graft mainly depends on the preoperative vascular condition of the recipient's cornea. Whereas transplants placed into avascular recipient beds enjoy long-term survival rates of > 90%, survival rates significantly decrease in pathologically pre-vascularized, so-called high-risk recipients, which account for around 10% of all performed transplants in Germany and > 75% in lower and middle-income countries worldwide. METHODS: This parallel-grouped, open-randomized, multicenter, prospective controlled exploratory investigator-initiated trial (IIT) intends to improve graft survival by preconditioning pathologically vascularized recipient corneas by (lymph)angioregressive treatment before high-risk corneal transplantation. For this purpose, corneal crosslinking (CXL) will be used, which has been shown to potently regress corneal blood and lymphatic vessels. Prior to transplantation, patients will be randomized into 2 groups: (1) CXL (intervention) or (2) no pretreatment (control). CXL will be repeated once if insufficient reduction of corneal neovascularization should be observed. All patients (both groups) will then undergo corneal transplantation. In the intervention group, remaining blood vessels will be additionally regressed using fine needle diathermy (on the day of transplantation). Afterwards, the incidence of graft rejection episodes will be evaluated for 24 months (primary endpoint). Overall graft survival, as well as regression of corneal vessels and/or recurrence, among other factors, will be analyzed (secondary endpoints). DISCUSSION: Based on preclinical and early pilot clinical evidence, we want to test the novel concept of temporary (lymph)angioregressive pretreatment of high-risk eyes by CXL to promote subsequent corneal graft survival. So far, there is no evidence-based approach to reliably improve graft survival in the high-risk corneal transplantation setting available in clinical routine. If successful, this approach will be the first to promote graft survival in high-risk transplants. It will significantly improve vision and quality of life in patients suffering from corneal blindness. TRIAL REGISTRATION: ClinicalTrials.gov NCT05870566. Registered on 22 May 2023.

Application of a Revised Tissue Saving Protocol for Combined Topography-Guided Photorefractive Keratectomy and Cross-Linking in a Cohort Having Pellucid Marginal Degeneration.

Purpose: To evaluate the efficiency, safety, and stability of a revised tissue-saving treatment protocol in a cohort having pellucid marginal degeneration (PMD). Methods: A retrospective cohort study was conducted on patients with PMD and no previous treatments. A revised protocol of topo-guided photorefractive keratectomy to be followed by customized phototherapeutic keratectomy and then corneal crosslinking was evaluated by comparing the pre and postoperative outcomes regarding visual (subjective refraction) and topographic (using data from Sirius CSO topography software) outcomes. Results: There were both statistically significant and clinically relevant improvements in the postoperative parameters, where each of the unaided and corrected visual acuity, spherical equivalent, refractive cylinder, K readings, topographic cylinder, inferior minus superior difference at the 2- and 4- mm diameters, coma aberration, and higher order aberrations were significantly better postoperatively (all p values were less than 0.01, except for maximum k readings where the p-value was 0.017). The safety and efficacy indices for the surgical procedure were remarkably high (1.53 ± 0.70 and 0.90 ± 0.32, respectively). Conclusion: Our proposed tissue-saving protocol (which showed satisfactory results in keratoconus cases according to a previously published article by our research team) has proven its successful outcomes (both topographically and visually) in cases of PMD, which is a rare ectatic entity with guarded prognosis using the available conventional ectasia treatment modalities.

Late-Onset Haze and Severe Corneal Flattening after Combined Corneal Collagen Cross-Linking and Photorefractive Keratectomy (CXL Plus): A Case Report.

Introduction: Significant corneal flattening and haze are important complications that can occur after combined corneal collagen cross-linking (CXL) and photorefractive keratectomy (PRK) procedures (CXL Plus). Case Presentation: We present a 24-year-old man who underwent combined standard CXL and PRK. The patient experienced satisfactory vision for approximately 4 years after the surgery. However, after this period, he began to complain of visual blurring. Subsequent examination revealed significant corneal haze, excessive flattening in both eyes, and thinning (thinnest point 227 µm in the right eye, 244 µm in the left eye) 4 years postoperatively. Upon presentation, the corrected distance visual acuity (CDVA) was 20/200 in the right eye and 20/400 in the left eye. The presenting refraction was +2.50 sph, -3.50 cyl *114 in the right eye and +11.5 sph, -9.75 cyl *81 in the left eye. With rigid gas permeable contact lenses, the corrected visual acuity was 20/50 in both eyes. Before the CXL Plus surgery, initial refraction and CDVA were 20/50 in the right eye (-5.50 sph, -3.00 cyl *175) and 20/30 in the left eye (-5.50 sph, -2.75 cyl *175). The patient was treated by penetrating keratoplasty. The CDVA reached 20/30 at the final follow-up. Conclusion: Our report highlights significant corneal haze and flattening that occurred 4 years after combined CXL and PRK treatment. These findings suggest that this procedure might not be safe in suspected patients of keratoconus. Further long-term follow-up research is necessary to evaluate the safety of combined CXL and PRK procedures.

Effect of accelerated high-fluence riboflavin and rose bengal-mediated corneal cross-linking on resistance to enzymatic digestion.

PURPOSE: This study evaluated the effect of high-fluence accelerated corneal cross-linking on the resistance to enzymatic digestion, assessing two chromophore/light combinations: riboflavin/UV-A light (RF/UV-A) and rose bengal/green light (RB/green). METHODS: Freshly prepared ex-vivo porcine corneas (n = 189) were divided into 8 groups groups. Group A corneas were unirradiated controls without chromophore soaking (A0), or soaked with riboflavin (A1) or rose bengal (A2). Group B corneas underwent accelerated epi-off RF/UV-A CXL at fluences of 5.4 J/cm² (B1), 10 J/cm² (B2), or 15 J/cm² (B3). Group C corneas underwent accelerated epi-off RB/green CXL at fluences of either 10 J/cm² (C1) or 15 J/cm² (C2). Following CXL, all corneas were digested in 0.3% collagenase-A solution, and the time until complete dissolution was measured. RESULTS: Non-irradiated controls exposed to RF and RB enhanced corneal resistance to collagenase digestion, with RB having a stronger effect than RF. RF/UV-A-treated corneas showed significantly increased digestion resistance with increasing fluence levels. RB/green-treated corneas displayed enhanced digestion resistance with each increase in fluence up to 10 J/cm²; a 15 J/cm² fluence yielded similar digestion resistance times to a 10 J/cm² fluence, suggesting a plateau effect in accelerated RB/green CXL protocols. CONCLUSIONS: When compared to standard-fluence treatments, high-fluence accelerated epi-off CXL using both riboflavin and rose bengal significantly increases resistance to enzymatic digestion. The optimal settings for clinical protocols might be 15 J/cm² (30 mW/cm² for 8 min 20 s) for RF/UV-A and 10 J/cm² (15 mW/cm² for 11 min 7 s) for RB/Green Light.

Fungal Keratitis: Diagnosis, Management, and Recent Advances.

Fungal keratitis is one of the major causes of microbial keratitis that may lead to corneal blindness. Many problems related to diagnosis and therapy are encountered in fungal keratitis, including difficulty in obtaining laboratory diagnoses and the availability and efficacy of antifungal medications. Intensive and prolonged use of antifungal topical preparations may not be enough. The use of antifungal medications is considered the main treatment for fungal keratitis. It is recommended to start antifungal therapy after confirmation of the clinical diagnosis with a smear or positive cultures. Topical application of antifungal medications is a mainstay for the treatment of fungal keratitis; however, systemic, intra-stromal, or intra-cameral routes may be used. Therapeutic keratoplasty is the main surgical procedure approved for the management of fungal keratitis with good success rate. Intrastromal corneal injection of antifungal medications may result in steady-state drug levels within the corneal tissue and prevent intervals of decreased antifungal drug concentration below its therapeutic level. In cases of severe fungal keratitis with deep stromal infiltration not responding to treatment, intracameral injection of antifungal agents may be effective. Collagen cross-linking has been proposed to be beneficial for cases of fungal keratitis as a stand-alone therapy or as an adjunct to antifungal medications. Although collagen cross-linking has been extensively studied in the past few years, its protocol still needs many modifications to optimize UV fluence levels, irradiation time, and concentration of riboflavin to achieve 100% microbial killing.

Evaluation of risk factors for treatment failure in canine patients undergoing photoactivated chromophore for keratitis - corneal cross-linking (PACK-CXL): a retrospective study using additive bayesian network analysis.

BACKGROUND: Infectious keratitis is a common ophthalmic condition in canine patients. Sequelae can include keratomalacia and corneal perforation, a vision threatening outcome. Photoactivated chromophore for keratitis - corneal cross-linking (PACK-CXL) is a non-surgical, adjunctive treatment method for infectious keratitis. The goal of this retrospective, multicenter study was to determine risk factors for treatment failure following PACK-CXL in canine patients suffering from suspected infectious keratitis. Medical records from four veterinary ophthalmology services were reviewed, and information related to patient demographics, ophthalmic findings, the PACK-CXL protocol used, and epithelialization time was collected and analyzed. Due to the potential for intervariable relationships, an additive Bayesian network (ABN) analysis was performed to evaluate these complex relationships. RESULTS: Records for 671 eyes (668 dogs) were included in the analysis. Based on the ABN, in the population included here, patients who underwent an accelerated PACK-CXL protocol were less likely to experience treatment failure versus patients treated with a slow protocol. Mutual dependencies between exposure variables were identified by ABN, which would have been overlooked using classical regression. Corneal re-epithelialization time was shortened following PACK-CXL combined with topical medical therapy compared to PACK-CXL alone. CONCLUSIONS: No risk factors associated with treatment failure were identified in the population included in the present study. Canine patients may benefit from the use of accelerated PACK-CXL protocols, especially when combined with topical antibiotics and anti-collagenolytic therapy. The reasons for this apparent positive impact on treatment outcome remain unclear.

Photoactivated chromophore-corneal cross-linking accelerates corneal healing in fungal keratitis: an updated meta-analysis.

AIM: To determine the effectiveness and safety of photoactivated chromophore-corneal cross-linking (PACK-CXL) adjuvant in infectious keratitis by April 5, 2022. METHODS: We searched randomized controlled trials (RCTs) comparing standard antibiotic treatment (SAT) plus PACK-CXL to SAT in infectious keratitis in Embase, MEDLINE with PubMed, Web of Science, and Cochrane Library. We independently screened and extracted data using predesigned tables. Cochrane's risk-of-bias tool was utilized to examine the quality of RCTs. A random-effects model was employed to determine the overall effect size of the meta-analyses. Grading of Recommendations, and Assessment, Development and Evaluations (GRADE) was also performed to examine the quality of evidence. RESULTS: Seven eligible RCTs with 283 patients were acquired. Adjuvant PACK-CXL reduced the time needed to perform corneal healing in fungal keratitis (- 1.33 months; 95% CI, - 1.83 to - 0.42, I2 = 0%, P < 0.05) as compared to SAT alone. The risks of adverse events were not significantly different both in fungal and bacterial keratitis. Due to the substantial heterogeneity among studies, such as population, the type and severity of infectious keratitis, drug regimens of SAT, PACK-CXL protocol, and the judgment of subjective outcomes, the evidence grade was low. CONCLUSION: Adjuvant PACK-CXL accelerates fungal keratitis healing as compared to SAT alone. But more rigorous RCTs are required to determine the clinical effectiveness and safety.

Optomechanical assessment of photorefractive corneal cross-linking via optical coherence elastography.

Purpose: Corneal cross-linking (CXL) has recently been used with promising results to positively affect corneal refractive power in the treatment of hyperopia and mild myopia. However, understanding and predicting the optomechanical changes induced by this procedure are challenging. Methods: We applied ambient pressure modulation based optical coherence elastography (OCE) to quantify the refractive and mechanical effects of patterned CXL and their relationship to energy delivered during the treatment on porcine corneas. Three different patterned treatments were performed, designed according to Zernike polynomial functions (circle, astigmatism, coma). In addition, three different irradiation protocols were analyzed: standard Dresden CXL (fluence of 5.4 J/cm2), accelerated CXL (fluence of 5.4 J/cm2), and high-fluence CXL (fluence of 16.2 J/cm2). The axial strain distribution in the stroma induced by ocular inflation (Δp = 30 mmHg) was quantified, maps of the anterior sagittal curvature were constructed and cylindrical refraction was assessed. Results: Thirty minutes after CXL, there was a statistically significant increase in axial strain amplitude (p < 0.050) and a reduction in sagittal curvature (p < 0.050) in the regions treated with all irradiation patterns compared to the non-irradiated ones. Thirty-6 hours later, the non-irradiated regions showed compressive strains, while the axial strain in the CXL-treated regions was close to zero, and the reduction in sagittal curvature observed 30 minutes after the treatment was maintained. The Dresden CXL and accelerated CXL produced comparable amounts of stiffening and refractive changes (p = 0.856), while high-fluence CXL produced the strongest response in terms of axial strain (6.9‰ ± 1.9‰) and refractive correction (3.4 ± 0.9 D). Tripling the energy administered during CXL resulted in a 2.4-fold increase in the resulting refractive correction. Conclusion: OCE showed that refractive changes and alterations in corneal biomechanics are directly related. A patient-specific selection of both, the administered UV fluence and the irradiation pattern during CXL is promising to allow customized photorefractive corrections in the future.

Progressive high-fluence epithelium-on accelerated corneal crosslinking: a novel corneal photodynamic therapy for early progressive keratoconus.

Purpose: To assess the preliminary clinical results of a new, progressively higher fluence-pulsed light Epi-On accelerated crosslinking nomogram (PFPL M Epi-On ACXL) in the treatment of progressive keratoconus (KC). Setting: Siena Crosslinking Center, Siena, Italy. Methods: A prospective pilot open, non-randomized interventional study, including 32 eyes of 32 young-adult patients over 26 years old with Stages I-III progressive KC undergoing PFPL M Epi-On ACXL, was conducted. Riboflavin loading was performed by using Paracel I 0.25% for 4 min and Paracel II 0.22% for 6 min. The Avedro KXL System (Glaukos-Avedro, Burlington, USA) was used for pulsed-light accelerated crosslinking (ACXL) at air room 21% oxygenation and 13 min of UV-A irradiation. The treatment fluence was set at 7.2 J/cm2, 8.6 J/cm2, and 10.0 J/cm2 in corneas with baseline pachymetry <420 µm (group 1: 8 eyes), ≥ 420 µm <460 µm (group 2, 11 eyes), and ≥ 460 µm (group 3, 13 eyes), respectively. Uncorrected distance visual acuity (UDVA), best-spectacle corrected visual acuity (BSCVA), Scheimpflug corneal tomography, and anterior segment OCT (AS-OCT) data were collected at baseline and postoperatively at 1, 3, and 6 months. Results: UDVA and BSCVA improved in all groups (P ≤ 0.05). Maximum keratometry values (K max) showed a significant decrease in the 10.0 J/cm2 group (Δ -1.68 D). The coma (HOAs) value improved significantly by the sixth month in all groups. OCT average demarcation lines were 211 ± 19 µm in group 1, 245 ± 23 µm in group 2, and 267 ± 21 µm in group 3. Conclusions: The preliminary results show that pachymetry-based PFPL M Epi-On ACXL nomogram stabilizes ectasia progression. Higher fluence Epi-On ACXL increases CXL penetration, with better functional outcomes in the absence of complications.

Accelerated high fluence photoactivated chromophore for infectious keratitis-corneal cross-linking (PACK-CXL) at the slit lamp: a pilot study.

Introduction: Photoactivated Chromophore for Infectious Keratitis-Corneal Cross-Linking (PACK-CXL) has garnered substantial interest among researchers and ophthalmologists due to its high promise as a potential treatment for infectious keratitis. The aim of this study is to evaluate the efficacy and safety of high fluence PACK-CXL, using 10.0 J/cm2 (30 mW/cm2, 5 min, and 33 s) at the slit lamp. Methods: This prospective interventional, nonrandomized cohort study included 20 eyes of 20 patients with bacterial, fungal, or mixed origin keratitis who underwent high fluence PACK-CXL treatment as an adjunct therapy to conventional antimicrobial therapy per American Academy of Ophthalmology treatment guidelines. The re-epithelization time was recorded, and corneal endothelial cell density was counted before and after treatment. Results: The average re-epithelization time was 8.2 ± 2.8 days (range 3-14 days). After PACK-CXL treatment, eight patients (40%) were directly discharged, while the remained patients stayed in the hospital for an average of 5.6 ± 3.5 days. No eyes required keratoplasty. Endothelial cell density counts before and after the PACK-CXL procedure were 2,562.1 ± 397.3, and 2,564.8 ± 404.5 cells/mm2, respectively (p = 0.96). Conclusion: although it was not a randomized control trial, we conclude that high fluence PACK-CXL as an adjuvant therapy is safe with no complications observed, and efficient as time to re-epithelization was less than 14 days for all patients and no patients underwent tectonic keratoplasties. Further research is needed to compare it to the current standard of care.

Outcomes of topography-guided PRK/CXL in keratoconus using the NIDEK CXIII system-"Bharat Protocol" (Pilot study).

Purpose: Outcome of topography-guided excimer laser ablation in conjunction with accelerated, high-fluence cross-linking in corneal ecstatic disease using the NIDEK CXIII equipped with CATz algorithm from the FinalFit software-"Bharat Protocol." Methods: Retrospective case record review of 30 eyes of 17 patients of stage 1-3 keratoconus who underwent the procedure was performed. Data collected were for visual acuity, distortion-induced eye pain, and keratometry. Pachymetry, lower order and higher order aberrations, spherical aberrations, and topographic cylinder were documented from by Scheimpflug imaging (Pentacam 70700: Oculus, Wetzlar, Germany). Results: At a minimum follow-up of 6 months (range 6.2-13 months), there was significant improvement in UCVA (P < 0.00001), BCVA (P = 0.0061), decrease in Kmax (P = 0.0349), Ksteep (P < 0.0411), Kflat (P = 0.0099), and pachymetry (P = 0.0001). Significant improvement was also seen in distortion-induced eye pain (27/30 to 2/30; P < 0.00001). A more than two-line improvement in UCVA and BCVA was seen in 23/30 and 17/30 cases, respectively. Ectasia was stabilized in all cases at the last follow-up, and no complications were seen. Conclusions: The "Bharat" Protocol to arrest keratectasia progression and improve corneal regularity is a safe and efficacious alternative as a keratoconus management option. This is the first such study on Nidek Platform for the same.

Development and validation to predict visual acuity and keratometry two years after corneal crosslinking with progressive keratoconus by machine learning.

Purpose: To explore and validate the utility of machine learning (ML) methods using a limited sample size to predict changes in visual acuity and keratometry 2 years following corneal crosslinking (CXL) for progressive keratoconus. Methods: The study included all consecutive patients with progressive keratoconus who underwent CXL from July 2014 to December 2020, with a 2 year follow-up period before July 2022 to develop the model. Variables collected included patient demographics, visual acuity, spherical equivalence, and Pentacam parameters. Available case data were divided into training and testing data sets. Three ML models were evaluated based on their performance in predicting case corrected distance visual acuity (CDVA) and maximum keratometry (Kmax) changes compared to actual values, as indicated by average root mean squared error (RMSE) and R-squared (R2) values. Patients followed from July 2022 to December 2022 were included in the validation set. Results: A total of 277 eyes from 195 patients were included in training and testing sets and 43 eyes from 35 patients were included in the validation set. The baseline CDVA (26.7%) and the ratio of steep keratometry to flat keratometry (K2/K1; 13.8%) were closely associated with case CDVA changes. The baseline ratio of Kmax to mean keratometry (Kmax/Kmean; 20.9%) was closely associated with case Kmax changes. Using these metrics, the best-performing ML model was XGBoost, which produced predicted values closest to the actual values for both CDVA and Kmax changes in testing set (R2 = 0.9993 and 0.9888) and validation set (R2 = 0.8956 and 0.8382). Conclusion: Application of a ML approach using XGBoost, and incorporation of identifiable parameters, considerably improved variation prediction accuracy of both CDVA and Kmax 2 years after CXL for treatment of progressive keratoconus.

The relationship between keratan sulfate glycosaminoglycan density and mechanical stiffening of CXL treatment.

The corneal stroma is primarily composed of collagen fibrils, proteoglycans, and glycosaminoglycans (GAGs). It is known that corneal crosslinking (CXL) treatment improves mechanical properties of the cornea. However, the influence of stromal composition on the strengthening effect of CXL procedure has not been thoroughly investigated. The primary objective of the present research was to characterize the effect of keratan sulfate (KS) GAGs on the efficacy of CXL therapy. To this end, the CXL method was used to crosslink porcine corneal samples from which KS GAGs were enzymatically removed by keratanase II enzyme. Alcian blue staining was done to confirm the successful digestion of GAGs and uniaxial tensile experiments were performed for characterizing corneal mechanical properties. The influence of GAG removal and CXL treatment on resistance of corneal samples against enzymatic pepsin degradation was also quantified. It was found that removal of KS GAGs significantly softened corneal tensile properties (P < 0.05). Moreover, the CXL therapy significantly increased the tensile stiffness of GAG-depleted strips (P < 0.05). GAG-depleted corneal buttons were dissolved in the pepsin digestion solution significantly faster than control samples (P < 0.05). The CXL treatment significantly increased the time needed for complete pepsin digestion of GAG-depleted disks (P < 0.05). Based on these observations, we concluded that KS GAGs play a significant role in defining tensile properties and structural integrity of porcine cornea. Furthermore, the stiffening influence of the CXL treatment does not significantly depend on the density of corneal KS GAGs. The findings of the present study provided new information on the relation between corneal composition and CXL procedure mechanical effects.

Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study.

OBJECTIVE: The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK). PATIENTS AND METHODS: This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). RESULTS: Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes. CONCLUSION AND RECOMMENDATION: PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.

Long Term Corneal Flattening After Corneal Crosslinking in Patients with Progressive Keratoconus.

Purpose: We evaluate the long-term visual, refractive, and keratometric outcomes after corneal crosslinking (CXL) in patients with progressive keratoconus (KC) and the incidence of an extreme corneal flattening effect. Settings: Oftalmosalud Institute of Eyes, Lima, Perú. Design: Retrospective cohort study. Methods: Forty-five eyes that underwent CXL with epithelial removal between June 2006 and September 2011. Data analysis was performed at preoperative evaluation, 1 year postoperatively, and at least 10 years or more postoperatively. Outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and Scheimpflug (Pentacam) analysis. Progression was defined by an increase in steep keratometry (Ks) of 1.5D or greater between 2 examinations. Extreme flattening effect was defined as a decrease in K values equal to or greater than 5 diopters (D). Results: Mean follow-up time was 11 ± 1.07 years (range 10-13 years). There was a significant improvement in Ks, UCVA, CDVA, and spherical equivalent at the last visit. The overall rate of progression was 2.22% (1/45). Extreme flattening was observed in 15.5% (7/45) of the eyes, and this was associated with a loss of CDVA in 4.44% (2/45) of the eyes. One eye with corneal flattening of 11.5 D lost 7 lines of CDVA and required corneal transplantation. Conclusion: CXL is a safe and effective procedure to stop the progression of KC with a good overall long-term success rate. Extreme corneal flattening may be more common than commonly recognized, and severe corneal flattening associated with a decrease in CDVA may occur.