Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats.

Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea's collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.

Deep learning for detection of Fuchs endothelial dystrophy from widefield specular microscopy imaging: a pilot study.

BACKGROUND: To describe the diagnostic performance of a deep learning (DL) algorithm in detecting Fuchs endothelial corneal dystrophy (FECD) based on specular microscopy (SM) and to reliably detect widefield peripheral SM images with an endothelial cell density (ECD) > 1000 cells/mm2. METHODS: Five hundred and forty-seven subjects had SM imaging performed for the central cornea endothelium. One hundred and seventy-three images had FECD, while 602 images had other diagnoses. Using fivefold cross-validation on the dataset containing 775 central SM images combined with ECD, coefficient of variation (CV) and hexagonal endothelial cell ratio (HEX), the first DL model was trained to discriminate FECD from other images and was further tested on an external set of 180 images. In eyes with FECD, a separate DL model was trained with 753 central/paracentral SM images to detect SM with ECD > 1000 cells/mm2 and tested on 557 peripheral SM images. Area under curve (AUC), sensitivity and specificity were evaluated. RESULTS: The first model achieved an AUC of 0.96 with 0.91 sensitivity and 0.91 specificity in detecting FECD from other images. With an external validation set, the model achieved an AUC of 0.77, with a sensitivity of 0.69 and specificity of 0.68 in differentiating FECD from other diagnoses. The second model achieved an AUC of 0.88 with 0.79 sensitivity and 0.78 specificity in detecting peripheral SM images with ECD > 1000 cells/mm2. CONCLUSIONS: Our pilot study developed a DL model that could reliably detect FECD from other SM images and identify widefield SM images with ECD > 1000 cells/mm2 in eyes with FECD. This could be the foundation for future DL models to track progression of eyes with FECD and identify candidates suitable for therapies such as Descemet stripping only.

Neuropathic Corneal Pain: Tear Proteomic and Neuromediator Profiles, Imaging Features, and Clinical Manifestations.

PURPOSE: To investigate the tear proteomic and neuromediator profiles, in vivo confocal microscopy (IVCM) imaging features, and clinical manifestations in neuropathic corneal pain (NCP) patients. DESIGN: Cross-sectional study. METHODS: A total of 20 NCP patients and 20 age-matched controls were recruited. All subjects were evaluated by corneal sensitivity, Schirmer test, tear break-up time, and corneal and ocular surface staining, Ocular Surface Disease Index and Ocular Pain Assessment Survey questionnaires were administered, as well as IVCM examinations for corneal nerves, microneruomas, and epithelial and dendritic cells. Tears were collected for neuromediator and proteomic analysis using enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. RESULTS: Burning and sensitivity to light were the 2 most common symptoms in NCP. A total of 188 significantly dysregulated proteins, such as elevated metallothionein-2, creatine kinases B-type, vesicle-associated membrane protein 2, neurofilament light polypeptide, and myelin basic protein, were identified in the NCP patients. The top 10 dysregulated biological pathways in NCP include neurotoxicity, axonal signaling, wound healing, neutrophil degradation, apoptosis, thrombin signaling mitochondrial dysfunction, and RHOGDI and P70S6K signaling pathways. Compared to controls, the NCP cohort presented with significantly decreased corneal sensitivity (P < .001), decreased corneal nerve fiber length (P = .003), corneal nerve fiber density (P = .006), and nerve fiber fractal dimension (P = .033), as well as increased corneal nerve fiber width (P = .002), increased length, total area and perimeter of microneuromas (P < .001, P < .001, P = .019), smaller corneal epithelial size (P = .017), and higher nerve growth factor level in tears (P = .006). CONCLUSIONS: These clinical manifestations, imaging features, and molecular characterizations would contribute to the diagnostics and potential therapeutic targets for NCP.

Effects of Different Capsulotomy and Fragmentation Energy Levels on the Generation of Oxidative Stress Following Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: This study was conducted to evaluate the effects of different capsulotomy and fragmentation energy levels on the production of oxidative free radicals following femtosecond laser-assisted cataract surgery (FLACS) with a low-energy platform. METHODS: The experimental study included 60 porcine eyes (12 groups). In each group, capsulotomies with 90% or 150% energy, and fragmentations with 90%, 100%, or 150% energy or 150% with high spot density, respectively, were performed. Control samples were obtained from non-lasered eyes at the beginning (five eyes) and end (five eyes) of the experiment. In the clinical study, 104 eyes were divided into 5 groups, and they received conventional phacoemulsification (20 eyes), FLACS with 90% capsulotomy and 100% fragmentation energy levels without NSAIDs (16 eyes), FLACS with 90% (26 eyes) or 150% (22 eyes) capsulotomy energy levels, respectively, with a 100% fragmentation energy level and NSAIDs, and FLACS with 90% capsulotomy and 150% fragmentation energy levels and NSAIDs (20 eyes). Aqueous samples were analyzed for their malondialdehyde (MDA) and superoxide dismutase (SOD) levels. RESULTS: In the experimental study, there were no significant differences in the MDA and SOD levels between the groups with different capsulotomy energy levels. An increase in the fragmentation energy from 100% to 150% led to significantly higher MDA levels in the groups with both 90% (p = 0.04) and 150% capsulotomy energy levels (p = 0.03), respectively. However, increased laser spot densities did not result in significant changes in MDA or SOD levels. In the clinical study, all four of the FLACS groups showed higher MDA levels than the conventional group. Similarly, the increase in the fragmentation energy from 100% to 150% resulted in significantly elevated levels of MDA and SOD, respectively. CONCLUSIONS: Although increasing the FSL capsulotomy energy level may not have increased free radicals, higher fragmentation energy levels increased the generation of aqueous free radicals. However, fragmentation with high spot density did not generate additional oxidative stress. Increased spot density did not generate additional oxidative stress, and this can be helpful for dense cataracts.

Surgical Technique to Treat Presbyopic Inlay-Associated Corneal Haze With Sequential Excimer Photoablation: A Case Series.

PURPOSE: To describe an approach using sequential excimer laser ablation of the stromal surface of the corneal flap with or without subsequent excimer ablation to the stromal bed to reduce presbyopic inlay-associated corneal haze. METHODS: Twelve patients who underwent KAMRA inlay (Acufocus) explantation due to corneal haze were included. The mean interval between explantation and the primary surgery (phototherapeutic keratotomy [PTK] to corneal flap) was 16.2 ± 29.7 months (range = 1 to 83 months). The corneal flap was lifted and laid on an evisceration spoon and an excimer laser was used to ablate the flap stroma by 30 to 40 µm depth. Subsequently, an excimer laser was used to ablate and treat the stromal bed following a second flap lift according to the manifest refraction, leaving a minimal residual stromal bed thickness of greater than 300 µm. For both procedures, mitomycin C 0.02% was applied to the stromal bed before the flap was replaced and a bandage contact lens applied. RESULTS: Reductions in corneal haze were observed, following PTK to the corneal flap with or without photorefractive keratectomy (PRK) to the stromal bed, both clinically and on imaging. No significant changes in uncorrected distance visual acuity (P = .442) and corrected distance visual acuity (P = .565) were observed. Improvements were observed for both spherical equivalent refractive errors (P = .036) and corneal light backscatter (P = .019). There were significant improvements in spherical aberrations (P = .014) but no changes in total lower and higher order aberrations. CONCLUSIONS: PTK to the corneal flap with or without subsequent stromal bed PRK is an effective technique in treating corneal haze following presbyopic inlay explantation. [J Refract Surg. 2023;39(9):639-646.].

Conjunctival transcriptomics in ocular mucous membrane pemphigoid.

PURPOSE: Ocular Mucous Membrane Pemphigoid (OcMMP) is an orphan disease characterized by chronic autoimmune-driven conjunctival inflammation leading to progressive scarring, debilitating symptoms, and blinding sequelae. This feasibility study aims to demonstrate conjunctival genetic transcriptomic analyses as a putative tool for interrogation of pathogenic signaling pathways in OcMMP. METHODS: Conjunctival RNA profiling using the NanoString nCounter Human Fibrosis panel was undertaken on RNA extracted from conjunctival swabs obtained from 6 MMP patients (8 eyes; 4 M/2F; median age 78 [range 64-84] years); and 8 age-matched control participants (15 eyes; 3 M/5F; median age 69.5 [range 69-88] years). Data from 770 genes were analyzed with ROSALIND HyperScale architecture and stratified according to the level of clinically visible bulbar conjunctival inflammation. Normalization, fold-changes (≥+1.5-fold or ≤ -1.5-fold) and p-values adjustment (<0.05) using the Benjamini-Hochberg method were calculated. RESULTS: 93 differentially expressed genes (DEGs) were observed between OcMMP versus controls of which 48 were upregulated, and 45 downregulated. The top 4 upregulated DEGs represented fibrosis (COL3A1, COL1A1, FN1 and THBS1) while the key under-expressed genes (SCIN, HMGS2, XCL1/2) were indicative of ocular surface failure (goblet cell loss, keratinization, vulnerability to secondary infections). Forty-four pathways had a global significance score ≥2, the most significant being those related to extracellular matrix (ECM) remodeling, synthesis, and degradation. These pathways were accentuated in eyes with visible inflammation. CONCLUSIONS: NanoString methodology acquired via a simple conjunctival swab identifies profibrotic genes in OcMMP group and differentiates inflamed eyes. Longitudinal sampling and following investigative intervention will further mechanistic insight and development of novel biomarkers to monitor disease progression.

Impact of Exposomes on Ocular Surface Diseases.

Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs.

Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy.

(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy. (2) Methods: Cell injections of corneal endothelial cells were performed in 45 eyes in a rabbit model of BK. AS-OCT imaging and central corneal thickness (CCT) measurement were performed at baseline and on day 1, day 4, day 7 and day 14 following cell injection. A logistic regression was modelled to predict successful corneal deturgescence and its failure with cell aggregate visibility and CCT. Receiver-operating characteristic (ROC) curves were plotted, and areas under the curve (AUC) calculated for each time point in these models. (3) Results: Cellular aggregates were identified on days 1, 4, 7 and 14 in 86.7%, 39.5%, 20.0% and 4.4% of eyes, respectively. The positive predictive value of cellular aggregate visibility for successful corneal deturgescence was 71.8%, 64.7%, 66.7% and 100.0% at each time point, respectively. Using logistic regression modelling, the visibility of cellular aggregates on day 1 appeared to increase the likelihood of successful corneal deturgescence, but this did not reach statistical significance. An increase in pachymetry, however, resulted in a small but statistically significant decreased likelihood of success, with an odds ratio of 0.996 for days 1 (95% CI 0.993-1.000), 2 (95% CI 0.993-0.999) and 14 (95% CI 0.994-0.998) and an odds ratio of 0.994 (95% CI 0.991-0.998) for day 7. The ROC curves were plotted, and the AUC values were 0.72 (95% CI 0.55-0.89), 0.80 (95% CI 0. 62-0.98), 0.86 (95% CI 0.71-1.00) and 0.90 (95% CI 0.80-0.99) for days 1, 4, 7 and 14, respectively. (4) Conclusions: Logistic regression modelling of cell aggregate visibility and CCT was predictive of successful corneal endothelial cell injection therapy.

Effects of Rho-Associated Kinase (Rock) Inhibitors (Alternative to Y-27632) on Primary Human Corneal Endothelial Cells.

(1) Rho-associated coiled-coil protein kinase (ROCK) signaling cascade impacts a wide array of cellular events. For cellular therapeutics, scalable expansion of primary human corneal endothelial cells (CECs) is crucial, and the inhibition of ROCK signaling using a well characterized ROCK inhibitor (ROCKi) Y-27632 had been shown to enhance overall endothelial cell yield. (2) In this study, we compared several classes of ROCK inhibitors to both ROCK-I and ROCK-II, using in silico binding simulation. We then evaluated nine ROCK inhibitors for their effects on primary CECs, before narrowing it down to the two most efficacious compounds-AR-13324 (Netarsudil) and its active metabolite, AR-13503-and assessed their impact on cellular proliferation in vitro. Finally, we evaluated the use of AR-13324 on the regenerative capacity of donor cornea with an ex vivo corneal wound closure model. Donor-matched control groups supplemented with Y-27632 were used for comparative analyses. (3) Our in silico simulation revealed that most of the compounds had stronger binding strength than Y-27632. Most of the nine ROCK inhibitors assessed worked within the concentrations of between 100 nM to 30 µM, with comparable adherence to that of Y-27632. Of note, both AR-13324 and AR-13503 showed better cellular adherence when compared to Y-27632. Similarly, the proliferation rates of CECs exposed to AR-13324 were comparable to those of Y-27632. Interestingly, CECs expanded in a medium supplemented with AR-13503 were significantly more proliferative in (i) untreated vs. AR-13503 (1 µM; * p < 0.05); (ii) untreated vs. AR-13503 (10 µM; *** p < 0.001); (iii) Y-27632 vs. AR-13503 (10 µM; ** p < 0.005); (iv) AR-13324 (1 µM) vs. AR-13503 (10 µM; ** p < 0.005); and (v) AR-13324 (0.1 µM) vs. AR-13503 (10 µM; * p < 0.05). Lastly, an ex vivo corneal wound healing study showed a comparable wound healing rate for the final healed area in corneas exposed to Y-27632 or AR-13324. (4) In conclusion, we were able to demonstrate that various classes of ROCKi compounds other than Y-27632 were able to exert positive effects on primary CECs, and systematic donor-match controlled comparisons revealed that the FDA-approved ROCK inhibitor, AR-13324, is a potential candidate for cellular therapeutics or as an adjunct drug in regenerative treatment for corneal endothelial diseases in humans.

Mesenchymal Stem Cell Exosomes as Immunomodulatory Therapy for Corneal Scarring.

Corneal scarring is a leading cause of worldwide blindness. Human mesenchymal stem cells (MSC) have been reported to promote corneal wound healing through secreted exosomes. This study investigated the wound healing and immunomodulatory effects of MSC-derived exosomes (MSC-exo) in corneal injury through an established rat model of corneal scarring. After induction of corneal scarring by irregular phototherapeutic keratectomy (irrPTK), MSC exosome preparations (MSC-exo) or PBS vehicle as controls were applied to the injured rat corneas for five days. The animals were assessed for corneal clarity using a validated slit-lamp haze grading score. Stromal haze intensity was quantified using in-vivo confocal microscopy imaging. Corneal vascularization, fibrosis, variations in macrophage phenotypes, and inflammatory cytokines were evaluated using immunohistochemistry techniques and enzyme-linked immunosorbent assays (ELISA) of the excised corneas. Compared to the PBS control group, MSC-exo treatment group had faster epithelial wound closure (0.041), lower corneal haze score (p = 0.002), and reduced haze intensity (p = 0.004) throughout the follow-up period. Attenuation of corneal vascularisation based on CD31 and LYVE-1 staining and reduced fibrosis as measured by fibronectin and collagen 3A1 staining was also observed in the MSC-exo group. MSC-exo treated corneas also displayed a regenerative immune phenotype characterized by a higher infiltration of CD163+, CD206+ M2 macrophages over CD80+, CD86+ M1 macrophages (p = 0.023), reduced levels of pro-inflammatory IL-1ß, IL-8, and TNF-α, and increased levels of anti-inflammatory IL-10. In conclusion, topical MSC-exo could alleviate corneal insults by promoting wound closure and reducing scar development, possibly through anti-angiogenesis and immunomodulation towards a regenerative and anti-inflammatory phenotype.

Atypical microbial keratitis.

Atypical microbial keratitis refers to corneal infections caused by micro-organisms not commonly encountered in clinical practice. Unlike infections caused by common bacteria, cases of atypical microbial keratitis are often associated with worse clinical outcomes and visual prognosis. This is due to the challenges in the identification of causative organisms with standard diagnostic techniques, resulting in delays in the initiation of appropriate therapies. Furthermore, due to the comparatively lower incidence of atypical microbial keratitis, there is limited literature on effective management strategies for some of these difficult to manage corneal infections. This review highlights the current management and available evidence of atypical microbial keratitis, focusing on atypical mycobacteria keratitis, nocardia keratitis, achromobacter keratitis, and pythium keratitis. It will also describe the management of two uncommonly encountered conditions, infectious crystalline keratopathy and post-refractive infectious keratitis. This review can be used as a guide for clinicians managing patients with such challenging corneal infections.

The Effects of High Energy Capsulotomy on Aqueous Cytokine Profiles and Pupil Size During Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To assess whether aqueous cytokine profiles and pupil size are altered when high capsulotomy energy is used in eyes undergoing femtosecond laser-assisted cataract surgery (FLACS), and if preoperative use of a topical non-steroidal anti-inflammatory drug (NSAID) has an effect on this. METHODS: This prospective study recruited 83 eyes (63 patients) that were allocated to four treatment groups: conventional phacoemulsification (n = 20 eyes); FLACS with 90% capsulotomy energy without NSAID pretreatment (n = 20 eyes); FLACS with 90% capsulotomy energy with NSAID pre-treatment (n = 21 eyes); and FLACS with 150% capsulotomy energy with NSAID pretreatment (n = 22 eyes). Aqueous humor was collected before and after phacoemulsification to assess cytokine profiles. Pupil size was measured before and after laser capsulotomy. RESULTS: FLACS increased aqueous concentrations of pros-taglandin E2 (PGE2), interferon γ (IFN-γ), and interleukin 6 (IL-6) compared to conventional phacoemulsification. However, when increasing capsulotomy energy from 90% to 150% (with topical NSAID pretreatment), there was no significant increase in aqueous concentrations of PGE2 (37.7 ± 21.7 vs 33.6 ± 27.6 pg/mL, P = .99), IFN-γ (3.6 ± 1.1 vs 3.6 ± 0.8 pg/mL, P = .99), or IL-6 (7.1 ± 2.9 vs 6.3 ± 2.4 pg/mL, P = .99). For 90% and 150% capsulotomy energy, there was significant miosis following laser capsulotomy. Increased PGE2 concentration was significantly correlated with a reduction in pupil area (r = -0.58, P < .001) and pupil diameter (r = -0.57, P < .001). However, when a topical NSAID was given preoperatively, there was no difference in the degree of miosis between the 90% and 150% capsulotomy energy groups. CONCLUSIONS: Pretreatment with a topical NSAID prevented a rise in PGE2, IFN-γ, and IL-6 levels and excessive miosis when a higher capsulotomy energy was used. When a topical NSAID is used preoperatively, it is safe to use higher capsulotomy energy settings (with a low pulse energy femtosecond laser system) to achieve a satisfactory capsulotomy. [J Refract Surg. 2022;38(9):587-594.].

"Endothelium-Out" and "Endothelium-In" Descemet Membrane Endothelial Keratoplasty (DMEK) Graft Insertion Techniques: A Systematic Review With Meta-Analysis.

Background: We evaluated the visual outcomes and complications of "endothelium-out" and "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques. Materials and Methods: Electronic searches were conducted in CENTRAL, Cochrane databases, PubMed, EMBASE, ClinicalTrials.gov. Study designs included clinical trials, comparative observational studies, and large case series (≥25 eyes). PRISMA guidelines were used for abstracting data and synthesis. Random-effects models were employed for meta-analyses. Results: 21,323 eyes (95 studies) were included. Eighty-six studies reported on "endothelium-out" techniques; eight studies reported on "endothelium-in" techniques. One study compared "endothelium-out" to "endothelium-in" techniques. Eighteen "endothelium-out" studies reported that 42.5-85% of eyes achieved best-corrected visual acuity (BCVA) ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 58.7% (95% CI 49.4-67.7%,15 studies). Three "endothelium-in" studies reported that 44.7-87.5% of eyes achieved BCVA of ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 62.4% (95% CI 33.9-86.9%). Pooled mean endothelial cell loss was lower in the "endothelium-in" studies (28.1 ± 1.3%, 7 studies) compared to "endothelium-out" studies (36.3 ± 6.9%,10 studies) at 6 months (p = 0.018). Graft re-bubbling rates were higher in the "endothelium-out" studies (26.2%, 95% CI 21.9-30.9%, 74 studies) compared to "endothelium-in" studies (16.5%, 95% CI 8.5-26.4%, 6 studies), although statistical significance was not reached (p = 0.440). Primary graft failure rates were comparable between the two groups (p = 0.552). Quality of evidence was considered low and significant heterogeneity existed amongst the studies. Conclusion: Reported rates of endothelial cell loss were lower in "endothelium-in" DMEK studies at 6 months compared to "endothelium-out" studies. Outcomes of "endothelium-in" techniques were otherwise comparable to those reported in "endothelium-out" studies. Given the technical challenges encountered in "endothelium-out" procedures, surgeons may consider "endothelium-in" techniques designed for easier intra-operative DMEK graft unfolding. "Endothelium-in" studies evaluating outcomes at longer time points are required before conclusive comparisons between the two techniques can be drawn.

Case Report: Peripheral Ulcerative Keratitis in Systemic Solid Tumour Malignancies.

Purpose: To describe a case series of peripheral ulcerative keratitis (PUK) as a paraneoplastic condition in three patients with known underlying systemic solid tumor malignancies. Observations: Three patients with different systemic malignancies (1 recurrent breast cancer, 1 metastatic thyroid cancer, and 1 metastatic gastric adenocarcinoma) were identified to have PUK with significant corneal stromal melt. Autoimmune and infective work up for other etiologies were all negative. They all responded well to topical steroids and intravenous methylprednisolone. One patient had recurrences of her PUK and required repeated amniotic grafts and tectonic keratoplasties before her corneal condition stabilized. Conclusions and Importance: PUK can be a rare manifestation of systemic solid tumor malignancies. Although PUK may not be an indicator of progression of the underlying malignancy, it can be sight-threatening. This case series highlights the necessity for clinicians to refer patients with systemic malignancies presenting with inflamed eyes for an early ophthalmological review. This facilitates the detection of this blinding disease, allowing for early therapeutic interventions and potentially better visual outcomes for these patients.

Drug induced cicatrizing conjunctivitis: A case series with review of etiopathogenesis, diagnosis and management.

Drug induced cicatrizing conjunctivitis (DICC) is defined as a disease in which conjunctival cicatrization develops as a response to the chronic use of inciting topical and, rarely, systemic medications. DICC accounts for up to one third of cases of pseudopemphigoid, a large group of cicatrizing conjunctival diseases sharing similar clinical features to those of mucous membrane pemphigoid (MMP) but generally without the morbidity of progressive scarring or the need for systemic immunosuppression. The preservatives in topical anti-glaucoma medications (AGM) are the most frequently implicated inciting causes of DICC although topical antivirals, vasoconstrictors and mydriatics and some systemic drugs have been implicated. The literature review summarizes the classification, epidemiology, etiopathogenesis, histopathology, clinical presentation, diagnosis, management, and treatment outcomes of DICC in the context of a case series of 23 patients (42 eyes) with AGM induced DICC, from India and the UK. In this series all subjects reacted to preserved AGM with one exception, who also reacted to non-preserved AGM. At diagnosis >70% of eyes showed punctal scarring, inflammation, and forniceal shortening. Pemphigoid studies were negative in the 19/23 patients in whom they were carried out. DICC can be classified as non-progressive, progressive with positive pemphigoid immunopathology or progressive with negative pemphigoid immunopathology. It is unclear whether progressive DICC is a stand-alone disease, or concurrent (or drug induced) ocular MMP. Progressive cases should currently be treated as ocular MMP. The diagnosis can be made clinically when there is rapid resolution of symptoms and inflammation, usually within 1-16 weeks, after withdrawal of suspected inciting medications, ideally by temporary substitution of oral carbonic anhydrase inhibitors. If the response to withdrawal is uncertain, or the progression of inflammation and scarring continues then patients must be evaluated to exclude concurrent (or drug induced) MMP, and other potential causes of CC, for which the treatment and prognosis is different. Management, in addition to withdrawing inciting medications, may require short-term treatment of conjunctival inflammation with steroids, treatment of associated corneal disease with contact lenses or surface reconstructive surgery, control of intra-ocular pressure with non-preserved AGM and, in some, surgery for glaucoma or for trichiasis and entropion.

Centration and Stability of Small-Aperture Intraocular Lens in Aberrated Eyes.

PURPOSE: To investigate the visual outcomes and postoperative stability of IC-8 intraocular lens (AcuFocus, Inc) implantation following femtosecond laser-assisted cataract surgery. METHODS: In this prospective study, the IC-8 IOL was implanted in the non-dominant eye of 12 patients. Centration and uncorrected and corrected distance, intermediate, and near visual acuities (UDVA, UIVA, UNVA, CDVA, CIVA, CNVA) were evaluated up to postoperative month 3 (POM3). Means ± standard deviations are reported in logMAR units. RESULTS: There were no significant differences in absolute, vertical, and horizontal centration postoperatively versus intraoperatively. From intraoperative to POM3, mean displacement was 0.17 ± 0.09 and 0.14 ± 0.07 mm (P = .52) relative to the capsulorhexis and 0.28 ± 0.22 and 0.25 ± 0.14 mm relative to the limbus (P = .62), respectively. Centration remained within the 1.36-mm IC-8 aperture. Excluding patients with ocular comorbidities, from preoperatively to POM3, UDVA improved significantly from 0.52 ± 0.39 to 0.20 ± 0.11 logMAR (P = .024), with an efficacy index of 0.80 ± 0.31. The safety index was 1.30 ± 0.40, with no adverse events experienced. At POM3, CDVA, UIVA, and UNVA of 0.04 ± 0.05, 0.27 ± 0.11, and 0.22 ± 0.10 logMAR were achieved, respectively. Binocularly, all achieved UDVA of 20/25 or better and UIVA and UNVA of N6 and better. CONCLUSIONS: The IC-8 IOL can attain good centration and positional stability up to POM3. It enables both extended depth of focus and tolerance to aberration, making it capable of achieving spectacle independence after surgery. [J Refract Surg. 2022;38(2):98-105.].

A Review of Clinical Disease Scoring Systems for Cicatricial Diseases of the Conjunctiva.

Cicatricial conjunctival diseases (CCDs), are a diverse group of ocular surface diseases characterized by chronic scarring of the conjunctiva. These diseases can cause significant ocular morbidity. They are life-long once acquired and can be debilitating, painful diseases leading to visual loss. A recent international consensus of ocular surface disease experts have placed emphasis on the need of validated clinical disease scoring systems for CCDs, important for the objective evaluation of disease severity, outcomes of therapies, and longitudinal monitoring of disease. This review aims to describe the various published clinical disease scoring systems available for CCDs and evaluates the benefits and limitations of each system. It can be used as a guide for clinicians managing patients with CCDs and for researchers evaluating potential therapies in clinical trials.

The effects of laser displacement on femtosecond laser-assisted conjunctival autograft preparation for pterygium surgery.

AIMS: To evaluate the effects of no-suction femtosecond laser (FSL) stability on conjunctival autograft (CAG) dissection in pterygium surgery. METHODS: Prospective analysis of 35 eyes from 34 subjects who underwent femtosecond laser-assisted pterygium surgery with the Ziemer Z8 laser (Ophthalmic Systems AG, Switzerland). Intraoperative absolute FSL displacements were measured and correlated with the duration and ease of CAG peel, CAG thickness, measured with intraoperative optical coherence tomography, and deviation from intended graft thickness. RESULTS: The median absolute FSL displacement was 22 µm (interquartile range [IQR] 14.7 to 60.8), while median vertical FSL displacement was 14.7 µm (IQR 7.3 to 44) and median horizontal FSL displacement was 22.0 µm (IQR 14.7 to 44). 65.7% had a grade 1 peel, 11.4% had grade 2 peel, 14.3% had grade 3 peel and 8.6% had grade 4 peel. The median duration of CAG peel was 5.4 seconds (IQR 3 to 21.4). The median CAG thickness was 69 µm (IQR 60.3 to 78.5), and the median deviation from targeted graft thickness was 9 µm (IQR 1 to 16). Eyes with more difficult peels and longer duration of CAG peels had significantly greater vertical FSL displacements (p = 0.04 and 0.02 respectively), but not horizontal displacement, age, ethnicity, CAG thickness or deviation from original thickness, compared to those with better quality and shorter duration peels. 1 eye (2.9%) had an incomplete CAG peel with a buttonhole and 2 eyes had graft tears (5.7%). CONCLUSION: Micro-displacements during the suction-free CAG preparation are common but they did not affect the quality of the CAG peel, duration of peel, or CAG thickness. However, vertical globe displacement during FSL-assisted CAG creation was significantly associated with a more difficult and longer CAG peel duration. This highlights the importance of the cornea traction suture fixation to ensure stability of the eye during FSL application.