The Pathophysiology of Keratoconus.

PURPOSE: Keratoconus is a progressive disease characterized by changes in corneal shape, resulting in loss of visual function. There remains a lack of comprehensive understanding regarding its underlying pathophysiology. This review aims to bridge this gap by exploring structural failures and inflammatory processes involved in the etiology and progression of keratoconus. METHODS: A literature review was conducted using PubMed and Google Scholar databases, screening for articles published in English using the keyword combinations of "keratoconus" with "pathophysiology," "pathology," "metabolism," "inflammatory," "oxidative stress," "cytokines," "enzymes," "collagen," and "cornea." Articles published between January 1, 1970, and June 1, 2023, were queried and reviewed, with greater emphasis placed on more recent data. Fifty-six relevant studies were examined to develop a thorough review of the pathophysiological mechanisms at play in keratoconus. RESULTS: Biomechanical structural failures in the cornea seem to be the primary militating factors in keratoconus etiology and progression. These include disruptions in the arrangement in the collagen lamellae, a decrease in collagen levels, a decrease in natural collagen crosslinking, and changes in lysosomal enzyme activity. Immunologic changes have also been identified in keratoconus, challenging the traditional view of the condition as noninflammatory. Elevated levels of proinflammatory cytokines like IL-1b, IL-6, IL-17, and TNF-α have been observed, along with increased apoptosis of keratocytes. Increased oxidative stress leads to the activation of collagenase and gelatinase enzymes. CONCLUSIONS: Keratoconus is a complex condition influenced by both structural defects and inflammatory processes. Understanding these mechanisms can inform clinical management and potentially lead to more effective treatments.

Prevalence of Keratoconus Based on Scheimpflug Corneal Tomography Metrics in a Pediatric Population From a Chicago-Based School Age Vision Clinic.

PURPOSE: Determine the pediatric prevalence of keratoconus (KC) using Scheimpflug corneal tomography. METHODS: A prospective observational study was done on subjects aged 3 to 18 years at the Princeton Vision Clinic, Chicago, IL. Scheimpflug tomography (Pentacam HR, OCULUS Optikgerate GmbH) scans (Belin/Ambrósio Enhanced Ectasia BAD3) yielded BAD Final D (Final D) and Back Elevation at the Thinnest Point (BETP) measurements. Criteria differentiating non-KC from KC suspects & KC were, Non-KC -Final D <2.00 in both eyes; KC suspect -Final D ≥2.00 and <3.00 in combination with BETP ≥18 µm for myopia and ≥28 µm for hyperopia/mixed astigmatism in at least one eye; and KC -Final D of ≥3.00 with BETP ≥18 µm for myopia or ≥28 µm for hyperopia/mixed astigmatism in at least one eye. Two thousand two hundred and six subjects were recorded, removing duplicate and poor-quality scans leaving 2007 subjects. RESULTS: Of 2007 subjects, six were classified as KC -prevalence of 1:334, three subjects were KC suspects -prevalence of 1:669, and total prevalence of KC suspects and KC was 1:223. CONCLUSION: The prevalence of KC in children is higher than previously reported, emphasizing the importance of sensitive screening for KC at its earliest manifestation as standard in pediatric comprehensive eye examinations.

Less Complex Contact Lens Required for a Patient With Keratoconus After Topography-Guided Photorefractive Keratectomy.

ABSTRACT: In this report, we discuss contact lens (CL) fitting in a patient with a history of keratoconus (KC), before and after undergoing topography-guided photorefractive keratectomy (TG PRK). Before TG PRK, the patient failed multiple CL modalities and reported difficulty with his habitual CLs and inadequate spectacle-corrected visual acuity to perform his activities of daily living. In this case, a collaborative, comprehensive approach to visual management in a patient with KC was used, and after TG PRK was performed to improve his corneal contour and symmetry, our patient was fit with a standard soft CL and additionally had improved spectacle-corrected visual acuity.

Long-Term Outcomes After Corneal Cross-linking for Progressive Keratoconus and Corneal Ectasia: A 10-Year Follow-Up of the Pivotal Study.

OBJECTIVES: To report on the topographic and visual outcomes 10 years after corneal cross-linking in patients with progressive keratoconus and corneal ectasia after refractive surgery. METHODS: Cross-sectional cohort study of an original, prospective, randomized, clinical trial. Patients treated in a single center cornea and refractive surgery practice as part of the U.S. pivotal trials, which led to the Food and Drug Administration approval of corneal cross-linking, were recruited for a 10-year follow-up examination. LogMar lines (LL) of uncorrected visual acuity (UCVA) and best spectacle--corrected visual acuity (BSCVA), maximum keratometry, and thinnest pachymetry were evaluated. In addition, the Belin ABCD progression display was used to determine progression (95% confidence interval) of the anterior curvature, posterior curvature, and corneal thickness of each individual eye included. RESULTS: Nineteen eyes of 13 patients treated with standard cross-linking returned for a 10-year follow-up examination. Mean maximum keratometry changed from 58.2±12.0 diopters (D) to 58.3±10.1 D, thinnest pachymetry changed from 440.6±51.6 µm to 442.3±54.4 µm, UCVA changed from 0.79±0.42 LL to 0.86±0.46 LL, and BSCVA changed from 0.38±0.26 LL to 0.33±0.34 LL, 10 years after cross-linking. Individually, 68.5% of the entire cohort, 81.8% of keratoconus eyes, and 50% of eyes with corneal ectasia remained topographically stable 10 years after standard cross-linking. CONCLUSIONS: In the entire cohort, visual acuity and topography remained stable 10 years after cross-linking. Over the long-term, eyes with keratoconus seem to be more stable than those with corneal ectasia.

Correlation of Manifest Refraction and Simulated Keratometry to Tomography Characteristics in Patients With Keratoconus.

OBJECTIVES: To report on baseline refractive and keratometric values and their correlation with tomographic characteristics of eyes with keratoconus (KC). METHODS: Retrospective chart review of patients treated in a single-center cornea and refractive surgery practice. Baseline topographic measurements were reviewed for 1,012 keratoconic eyes of 586 patients between 2008 and 2018. The manifest refraction, thinnest pachymetry (P thin ), corneal astigmatism (K astig ), and the maximum (K max ), steep (K steep ), flat (K flat ), and mean (K mean ) keratometry were analyzed. The location of K max (x, y) was used to determine central (<1 mm), paracentral (1-3 mm), pericentral (3-5 mm), or peripheral (>5 mm) cone locations. RESULTS: In the entire cohort, the mean manifest sphere was -2.2±4.4 diopters (D) and the cylinder was -3.2±2.3 D. In total, 48.6% of patients had against the rule (ATR) manifest astigmatism (M astig ). The average K astig was 3.8±2.7 D, and unlike the manifest axis, 50.2% of patients had with the rule (WTR) K astig . Patients with a K max less than 50 D had an M astig of -1.9±1.6 D, 45.9% of which was ATR M astig . With respect to baseline tomography measurements, K max , K steep , K flat , and K mean were 58.0±9.4, 50.6±6.5, 46.8±5.9, and 48.6±6.1 D, respectively. There was a weak correlation between K max and simulated keratometry (K steep , K flat , and K mean ) for patients with a K max less than 60 D. CONCLUSIONS: Simulated keratometry is poorly correlated with KC severity until the disease is more severe. M astig ≥2 D and ATR M astig were correlated with KC at all levels of severity. M astig ≥2 D and ATR M astig may serve as a simple, inexpensive, and widely available indicator for topographic analysis to identify possible KC and suggest further workup; however, further prospective studies are needed to confirm its utility.

Corneal tissue addition keratoplasty: new intrastromal inlay procedure for keratoconus using femtosecond laser-shaped preserved corneal tissue.

PURPOSE: To report results of Corneal Tissue Addition Keratoplasty (CTAK) for keratoconus (KC) and ectasia after laser in situ keratomileusis. SETTING: Cornea and refractive surgery practice. DESIGN: Single center, prospective, open label clinical trial. METHODS: 21 eyes of 18 patients underwent CTAK. A tissue inlay of preserved corneal tissue was cut to customized specifications with a femtosecond laser and placed in a laser-created channel in the host cornea. Postoperative uncorrected and corrected distance visual acuity (UDVA, CDVA), manifest refraction spherical equivalent (MRSE), topographic mean keratometry (Kmean), maximum keratometry (Kmax), and the point of maximum flattening (Kmaxflat) were measured. RESULTS: Average UDVA improved from 1.21 ± 0.35 logMAR lines (LL) (20/327) to 0.61 ± 0.25 LL (20/82) ( P < .001). Average CDVA improved from 0.62 ± 0.33 LL (20/82) to 0.34 ± 0.21 LL (20/43) ( P = .002), and average MRSE improved from -6.25 ± 5.45 diopters (D) to -1.61 ± 3.33 D ( P = .002). Individually, 20 eyes (95.2%) gained more than 2 lines of UDVA, with 10 eyes (47.6%) gaining more than 6 lines, and no eyes worsening. 12 eyes (57.1%) gained at least 2 lines of CDVA, with 1 eye worsening by more than 2 lines. At 6 months, average Kmean flattened by -8.44 D ( P = .002), Kmax flattened by -6.91 D ( P = .096), and mean Kmaxflat was -16.03 D. CONCLUSIONS: CTAK is a promising procedure to improve visual acuity and topography in patients with KC and ectasia.

Ocular Impression-Based Scleral Lens With Wavefront-Guided Optics for Visual Improvement in Keratoconus.

ABSTRACT: This case reports on the use of wavefront-guided (wfg) optics on custom ocular impression-based scleral lenses (IBSLs) for visual improvement in a patient with keratoconus (KC). A 28-year-old man with KC, who had previously failed a traditional, diagnostically fit scleral lens (tSL), was fit with IBSLs with traditional optics. Using a system that included a dot matrix on the IBSL and a wavefront aberrometer with pupil and dot registration software, a wfgIBSL was created. When compared with the IBSL, the wfgIBSL reduced the total higher-order root mean square (HORMS) 67% and 64% in the right and left eye, respectively, resulting in a 2-line improvement in best-contact lens visual acuity (BCLVA) for both eyes. This case demonstrates the successful creation and application of a wfgIBSL resulting in a stable lens, a reduction in HORMS, and an improvement in BCLVA, after failure with a diagnostically fit tSL.

Lipid Keratopathy Management With Therapeutic Scleral Lens Wear.

PURPOSE: To report on the use of scleral lens therapy for a patient with lipid keratopathy secondary to rigid gas permeable contact lens wear and ocular surface disease. METHODS: Case report and literature review. RESULTS: A 40-year-old man with a history of keratoconus and rigid gas permeable contact lens wear, resulting in corneal neovascularization and lipid keratopathy. The patient reported to our clinic with central lipid keratopathy secondary to rigid gas permeable lens wear and ocular surface disease. Given the density, central location, and subsequent visual limitations induced by lipid deposition and topographical irregularity, penetrating keratoplasty and scleral contact lens wear were discussed as possible treatment options. In this case, scleral lens wear provided both visual improvement and resolution of lipid keratopathy. After 3 years, the patient has remained stable, with significant visual improvement and near-complete resolution of lipid keratopathy. CONCLUSIONS: This case illustrates the use of scleral lens wear in the therapeutic management of lipid keratopathy secondary to rigid gas permeable lens wear and ocular surface disease. For patients limited by lipid keratopathy and topographical irregularity, scleral lens wear may be used to achieve both visual and therapeutic outcomes.

Descemetocele Management With Therapeutic Scleral Lens Wear.

OBJECTIVES: This case reports on the use of scleral lens therapy for a patient with a descemetocele secondary to exposure and neurotrophic keratopathy. METHODS: Case report and literature review. RESULTS: A 31-year-old man had undergone emergency surgery to repair a ruptured arteriovenous malformation resulting in left facial and trigeminal nerve palsies. The patient reported to our clinic with a central descemetocele secondary to exposure and neurotrophic keratopathy. Given the poor prognosis of a therapeutic penetrating keratoplasty in this case, the descemetocele was treated with therapeutic scleral lens wear. After 1 year, the patient has remained stable without corneal perforation. CONCLUSIONS: This case illustrates the use of extended scleral lens wear, followed by maintenance with daily scleral lens wear, to manage a descemetocele in a patient with neurotrophic and exposure keratopathy. For patients at high risk of postsurgical complications, therapeutic scleral lens wear may be used as an alternative or as a supplement to corneal transplantation and tarsorrhaphy in patients with descemetocele formation.

Corneal Haze After Transepithelial Collagen Cross-linking for Keratoconus: A Scheimpflug Densitometry Analysis.

PURPOSE: To quantitate corneal haze and analyze the postoperative time course of corneal haze after transepithelial corneal collagen cross-linking (TECXL) in patients with keratoconus. METHODS: Patients underwent TECXL and were randomized into 2 groups. One group received intraoperative riboflavin 0.10% every minute, and the second group received riboflavin 0.10% every 2 minutes during ultraviolet exposure. Scheimpflug densitometry was measured preoperatively, and at 1, 3, 6, and 12 months to assess the postoperative time course. Densitometry measurements were also correlated with visual acuity, pachymetry, and topography outcomes. RESULTS: Fifty-nine eyes of 43 patients with keratoconus were analyzed. Preoperative mean corneal densitometry was 20.45 ± 2.79. Mean densitometry increased at 1 month (22.58 ± 3.79; P < 0.001), did not significantly change between 1 and 3 months (22.64 ± 3.83; P = 0.8), and significantly improved between 3 and 12 months postoperatively (mean6 21.59 ± 3.39; P = 0.002, mean12 20.80 ± 3.27; P = 0.002). There was no difference between preoperative and 1-year densitometry measurements (P = 0.21). There was no significant difference between the 1-minute and 2-minute subgroups. In addition, corneal densitometry at either 3 months or 1 year did not correlate with uncorrected distance visual acuity (P = 0.4), corrected distance visual acuity (P = 0.1), or maximum keratometry (P = 0.5), 1 year after corneal collagen cross-linking (CXL). CONCLUSIONS: After TECXL, corneal haze increased slightly at 1 month, plateaued between 1 and 3 months, and returned to baseline between 3 and 12 months. In general, corneal haze in this study was substantially less than the haze previously reported for the standard cross-linking procedure. CXL-associated corneal haze did not correlate with the postoperative visual or topographic outcomes 1 year after CXL.

Corneal higher-order aberrations after crosslinking and intrastromal corneal ring segments for keratoconus.

PURPOSE: To assess anterior corneal higher-order aberrations (HOAs) after corneal crosslinking (CXL) and intrastromal corneal ring segments (Intacs) used adjunctively. SETTING: Cornea and refractive surgery practice. DESIGN: Prospective, randomized clinical trial. METHODS: One hundred fifty-eight eyes of 150 patients were randomized into 2 groups: concurrent, Intacs and CXL during the same session (n = 81), or sequential, Intacs followed by CXL 3 months later (n = 77). Outcomes included changes in total, coma, trefoil, and spherical anterior corneal HOA 6 months after Intacs/CXL. The change in anterior corneal HOAs was correlated with the change in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and topography indices of maximum keratometry (Kmax), maximum flattening keratometry (Kmaxflat), and inferior-superior (I-S) ratio. A subjective visual function questionnaire was also analyzed. RESULTS: UDVA, CDVA, Kmax, I-S, and Kmaxflat all improved 6 months after treatment (UDVA = -0.22 ± 0.34, P < .001; CDVA = -0.13 ± 0.24, P < .001; Kmax = -3.1 ± 3.0D, P < .001; I-S = -4.2 ± 5.0 diopters [D], P < .001; Kmaxflat = -7.9 ± 4.0 D, P < .001). Total anterior corneal HOA, vertical coma, and horizontal coma anterior corneal HOAs significantly improved by -1.05 ± 0.93 µm (P < .001), -1.53 ± 1.18 µm (P < .001), and -0.35 ± 0.57 µm (P < .001), respectively. Spherical anterior corneal HOAs increased by 0.24 ± 0.70 µm (P < .001) at 6 months after Intacs/CXL. The change in trefoil was not statistically significant (Ptrefoil0 = .06, Ptrefoil30 = .2). There were no significant differences between the changes in anterior corneal HOAs in the sequential and same-day Intacs/CXL groups. The change in total anterior corneal HOAs was correlated with Kmax, Kmaxflat, and the I-S ratio. There was no correlation between the change in anterior corneal HOAs and the change in visual acuity or visual function survey responses. CONCLUSIONS: Total, horizontal coma, and vertical coma anterior corneal HOAs improved after Intacs/CXL. Spherical anterior corneal HOAs increased postoperatively, and there was no change in trefoil. Improvement of anterior corneal HOAs did not correlate with visual acuity improvement or subjective visual satisfaction outcomes.

Incidence and associations of intracorneal ring segment explantation.

PURPOSE: To assess the incidence and motivating determinants of explantation of intracorneal ring segments (ICRS) (Intacs) used for the treatment of keratoconus and corneal ectasia. SETTING: Cornea and refractive surgery subspecialty practice. DESIGN: Retrospective case series. METHODS: Consecutive cases of ICRS implantation performed to treat keratoconus or corneal ectasia were reviewed to determine the number that were eventually explanted and the motivating factors for explantation. Cases were assigned to 1 of 2 groups: (1) medical complications requiring removal and (2) refractive/topographic problem, with the explantation being elective. The corrected distance visual acuity, uncorrected distance visual acuity, maximum keratometry, and inferior-superior topography power difference before and after ICRS removal were also evaluated. RESULTS: The ICRS were explanted from 35 eyes of 31 patients from a total cohort of 572 eyes (6.1%). Of these, 15 ICRS (2.6%) were removed for medical complications and 20 (3.5%) for refractive/topographic considerations. CONCLUSIONS: A large proportion of ICRS were generally well tolerated on a long-term basis. The incidence of explantation secondary to medical complications was low, with the most frequent complication being infiltration around the segment. Explantation was effective in ameliorating medical complications and can be effective in improving corneal topography and clinical outcomes in some cases.

Transepithelial corneal crosslinking for keratoconus.

PURPOSE: To evaluate outcomes of corneal crosslinking (CXL) using a transepithelial technique for the treatment of keratoconus. SETTING: Cornea and refractive surgery subspecialty practice. DESIGN: Prospective case series. METHODS: Transepithelial CXL was performed in keratoconic eyes using riboflavin 0.1% and topical anesthetic containing benzalkonium chloride to facilitate riboflavin diffusion through the epithelium. Eyes were randomized to receive riboflavin administration either every 1 minute or every 2 minutes during ultraviolet-A exposure at 3mW/cm2. The principal outcome was change in maximum keratometry (K) and secondary outcomes included uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean K, and comparison of randomized groups. RESULTS: Eighty-two eyes of 56 patients were treated. At 1 year, maximum K decreased significantly by 0.45 diopters (D) ± 1.94 (SD); it improved by 2.0 D or more in 11 eyes (13%) and worsened by 2.0 D or more in 4 eyes (5%). The mean UDVA significantly improved by 0.7 lines, whereas the CDVA improved by 0.2 lines. Two eyes showed both continued progression with loss of CDVA. Only the 1-minute subgroup showed significant improvements in maximum K (-0.73 D) and UDVA. Transient corneal erosion and epitheliopathy were reported in 21% of eyes. CONCLUSIONS: Transepithelial CXL resulted in significant improvements in maximum K and UDVA over 1 year. There was a suggestion that increased riboflavin dosing might improve procedure outcomes. Further study is required to determine the relative advantages and disadvantages of different transepithelial approaches to the standard CXL protocol with epithelial removal.