With the development and gradual dissemination of corneal collagen cross-linking (CXL) in the twenty-first century as an early treatment for keratoconus, the management paradigm has shifted to include a greater focus on complete refractive correction for these patients. Though supplemental hard contact lens therapy remains a mainstay of visual rehabilitation in keratoconus, there has been increasing appeal in a completely surgical approach by combining CXL with adjuvant refractive procedures to both halt the ectatic process and enhance functional visual outcomes. Collectively termed “CXL plus” procedures, several combined protocols have been studied to various degrees in conjunction with CXL, involving photorefractive keratectomy (PRK), transepithelial phototherapeutic keratectomy (PTK), conductive keratoplasty (CK), intrastromal corneal ring segments (ICRS) implantation, phakic intraocular lens (PIOL) implantation, or multiple of these techniques together. The scope of this review aims to encompass a summary of current CXL protocols and present the current status of studies involving adjunctive keratorefractive procedures combined with CXL. By discussing the results to date of these CXL plus protocols, we can assess what further areas of investigation are necessary within this field as the next step to optimizing treatment modalities and outcomes for our keratoconus patients, regardless of disease severity.

Purpose: Conjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection. Methods: We analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2. Results: Across all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2. Conclusions: Together, these results indicate that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.

To describe a case of corneal ulceration associated with dupilumab use for atopic dermatitis. A patient developed an inflammatory corneal ulcer 3 weeks after starting bi-weekly intravenous dupilumab therapy. Symptoms resolved with topical prednisolone and discontinuation of the systemic therapy with dupilumab. Dupilumab is known to cause ocular surface inflammation, but we report a novel association between dupilumab use and potentially sight-threatening corneal ulceration.

Purpose: To identify global gene expression changes in the corneal epithelium of keratoconus (KC) patients compared to non-KC myopic controls. Methods: RNA-sequencing was performed on corneal epithelium samples of five progressive KC and five myopic control patients. Selected results were validated using TaqMan quantitative PCR (qPCR) on 31 additional independent samples, and protein level validation was conducted using western blot analysis on a subset. Immunohistochemistry was performed on tissue microarrays containing cores from over 100 KC and control cases. WNT10A transcript levels in corneal epithelium were correlated with tomographic indicators of KC disease severity in 15 eyes. Additionally, WNT10A was overexpressed in vitro in immortalized corneal epithelial cells. Results: WNT10A was found to be underexpressed in KC epithelium at the transcript (ratio KC/control = 0.59, P = 0.02 per RNA-sequencing study; ratio = 0.66, P = 0.03 per qPCR) and protein (ratio = 0.07, P = 0.06) levels. Immunohistochemical analysis also indicated WNT10A protein was decreased in Bowman's layer of KC patients. In contrast, WNT10A transcript level positively correlated with increased keratometry (Kmax ρ = 0.57, P = 0.02). Finally, WNT10A positively regulated COL1A1 expression in corneal epithelial cells. Conclusions: A specific Wnt ligand, WNT10A, is reduced at the mRNA and protein level in KC epithelium and Bowman's layer. This ligand positively regulates collagen type I expression in corneal epithelial cells. The results suggest that WNT10A expression in the corneal epithelium may play a role in progressive KC.

Purpose. This study aims to correlate the clinical signs of keratoconus (KC) which include superficial apical scarring, Fleischer rings, and Vogt striae with best spectacle-corrected visual acuity (BSCVA) and corneal tomography findings.Patients and methods. A retrospective observational study. 72 consecutive KC patients seen by the senior author over the course of one year were included in this case series. Eyes with pellucid marginal degeneration, postrefractive ectasia, history of a corneal graft, prior corneal collagen cross-linking, intracorneal ring segments or hydrops were excluded from analysis. Subsequently, the final analysis included only treatment-naïve KC eyes with varying degrees of disease severity.Results. BSCVA with manifest refraction was 0.5 logMAR higher in eyes with apical scarring (p<0.001). Eyes with apical scarring had worse vision than eyes with Fleischer rings alone (0.43 logMAR higher in the former,p<0.009). Eyes with apical scarring had higher keratometry readings (K2 = 64.56 ± 12.89 D versus 49.07 ± 6.61 D,p<0.001); this was also true for eyes with Fleischer rings compared with ring-free eyes (K2 = 56.23 ± 11.52 D versus 48.91 ± 7.79 D,p<0.001) and eyes with Vogt striae (K2 = 56.19 ± 10.27 D versus 50.68 ± 9.21 D,p=0.01). Atopic disease was a risk factor for scarring: odds ratio (OR) = 2.87 (p=0.03). The OR of observing Fleischer rings in KC eyes was 12% per year (p=0.001). Additionally, each mm of corneal apex displacement from the pupillary center led to a 0.76 logMAR increase in visual acuity (p=0.001).Conclusion. The presence of apical scarring and Fleischer rings on biomicroscopy can aid the clinician in making the distinction between severe or long-standing disease (respectively). Apical scarring is a sign of advanced disease and is associated with worse BSCVA and tomography findings. Fleischer rings are markers of intermediate disease and their presence correlates with disease duration.