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.

Update on corneal crosslinking for keratoconus and corneal ectasia.

PURPOSE OF REVIEW: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations. RECENT FINDINGS: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients. SUMMARY: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.

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.

Corneal Crosslinking for Progressive Keratoconus and Corneal Ectasia: Summary of US Multicenter and Subgroup Clinical Trials.

Purpose: The multicenter studies reviewed were designed to evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus and corneal ectasia after laser refractive surgery. The results of these studies led to approval by the United States Food and Drug Agency for both conditions in 2016. This paper reviews these studies, as well as single-center substudies investigating other aspects of crosslinking outcomes. Methods: As part of prospective, randomized, controlled clinical trials, the treatment group received standard CXL, and the sham control group received only riboflavin ophthalmic solution. The primary efficacy criterion was maximum keratometry (Kmax) 1 year after CXL. Secondary outcomes were corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA). Safety and adverse events were analyzed. In single-center substudies, corneal topography, ocular aberrations, corneal haze measurements, corneal thickness, corneal biomechanics, subjective visual function, and outcomes predictors were also investigated. This paper presents a general review of the design and outcomes of crosslinking in these studies. Results: In the crosslinking treatment group, Kmax flattened by 1.6 diopters (D) and 0.7 D in eyes with keratoconus and ectasia, respectively. In both studies, there was continued progression in the control group. The CDVA improved by an average of 5.7 logMAR letters (LL) in the keratoconus treatment group and by 5.0 LL in the ectasia group. In both studies, corneal haze was the most frequently reported crosslinking-related adverse finding. This was most prominent at 1 month and generally returned to baseline between 3 and 12 months. In general, corneal topography, ocular aberrations, and subjective visual function improved after crosslinking. Conclusions: In the US multicenter trials, CXL was shown to be safe and effective in stabilizing Kmax, CDVA, and UDVA in eyes with progressive keratoconus or corneal ectasia. Translational Relevance: Corneal crosslinking was originally developed in the laboratory at the University of Dresden in the late 1990s. The combination of ultraviolet-A light and riboflavin was found to be the most effective of a number of different modalities tested to increase the biomechanical strength of the cornea. The clinical study design for the US multicenter clinical trials of crosslinking demonstrated the safety and effectiveness of this technique for treatment of progressive keratoconus and corneal ectasia, bringing this important advancement to patients in the United States.

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.

Corneal crosslinking and intracorneal ring segments for keratoconus: A randomized study of concurrent versus sequential surgery.

PURPOSE: To assess outcomes of corneal crosslinking (CXL) and intracorneal ring segments (ICRS) (Intacs) used adjunctively, and then compare the safety and efficacy of concurrent versus sequential surgery. SETTING: Cornea and refractive surgery subspecialty practice. DESIGN: Prospective randomized clinical trial. METHODS: Patients were randomized to one of two groups: ICRS first, immediately followed by CXL during the same session (n = 104), or ICRS followed by CXL 3 months later (n = 94). Outcomes included changes in maximum keratometry (K) and topographic inferior-superior (I-S) difference, maximum flattening of topographic K, and changes in uncorrected (UDVA) and corrected (CDVA) distance visual acuities. These were analyzed in the entire cohort, in the two randomized groups, and in subgroups stratified to ICRS size and placement. Patients were followed for 6 months. RESULTS: The study comprised 198 eyes of 198 patients. Overall, maximum K decreased by an average of 2.5 D, I-S difference improved by 3.9 D, and there was an average maximum flattening of -7.5 D. The UDVA improved by 2.0 logarithm of the minimum angle of resolution lines, on average, and the CDVA improved by 1.1 lines. There was no significant difference between the sequential and concurrent groups in any of the outcomes analyzed. There were 6 clinically significant adverse events. CONCLUSIONS: CXL and ICRS can be used adjunctively with substantial improvement in corneal topography, and with no increase in safety concerns over each procedure alone. Sequential and concurrent treatment with ICRS and CXL show equivalent outcomes. Both thicker segment size and single segment placement seem to result in greater topographic improvement.

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.

U.S. Multicenter Clinical Trial of Corneal Collagen Crosslinking for Treatment of Corneal Ectasia after Refractive Surgery.

PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of corneal ectasia after laser refractive surgery. DESIGN: Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS: One hundred seventy-nine subjects with corneal ectasia after previous refractive surgery. METHODS: The treatment group underwent standard CXL, and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES: The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry (K), comparing treatment with control groups. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS: In the crosslinking treatment group, the maximum K value decreased by 0.7 diopters (D) from baseline to 1 year, whereas there was continued progression in the control group (1.3 D difference between treatment and control, P < 0.0001). In the treatment group, the maximum K value decreased by 2.0 D or more in 14 eyes (18%) and increased by 2.0 D or more in 3 eyes (4%). The CDVA improved by an average of 5.0 logarithm of the minimum angle of resolution (logMAR) letters. Twenty-three eyes (32%) gained and 3 eyes (4%) lost 10 or more logMAR letters. The UDVA improved 4.5 logMAR letters. Corneal haze was the most frequently reported crosslinking-related adverse finding. CONCLUSIONS: Corneal collagen crosslinking was effective in improving the maximum K value, CDVA, and UDVA in eyes with corneal ectasia 1 year after treatment, with an excellent safety profile. CXL is the first approved procedure to diminish progression of this ectatic corneal process.

United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment.

PURPOSE: To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus. DESIGN: Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS: Patients with progressive keratoconus (n = 205). METHODS: The treatment group underwent standard CXL and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES: The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry value, comparing treatment with control group. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS: In the CXL treatment group, the maximum keratometry value decreased by 1.6 diopters (D) from baseline to 1 year, whereas keratoconus continued to progress in the control group. In the treatment group, the maximum keratometry value decreased by 2.0 D or more in 28 eyes (31.5%) and increased by 2.0 D or more in 5 eyes (5.6%). The CDVA improved by an average of 5.7 logarithm of the minimum angle of resolution (logMAR) units. Twenty-three eyes (27.7%) gained and 5 eyes lost (6.0%) 10 logMAR or more. The UDVA improved 4.4 logMAR. Corneal haze was the most frequently reported CXL-related adverse finding. There were no significant changes in endothelial cell count 1 year after treatment. CONCLUSIONS: Corneal collagen crosslinking was effective in improving the maximum keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year after treatment, with an excellent safety profile. Corneal collagen crosslinking affords the keratoconic patient an important new option to decrease progression of this ectatic corneal process.

Removal and Repositioning of Intracorneal Ring Segments: Improving Corneal Topography and Clinical Outcomes in Keratoconus and Ectasia.

PURPOSE: To evaluate the efficacy of removal and relocation of intracorneal ring segments for improving outcomes in treatment of keratoconus and corneal ectasia. METHODS: This is a retrospective case series conducted at a cornea and refractive surgery subspecialty practice setting. Patients with previous insertion of 2 intracorneal ring segments underwent surgical removal and repositioning of segments because of unsatisfactory visual and topographic outcomes. The principal outcomes included uncorrected and corrected visual acuities, manifest refraction, topography-derived maximum keratometry (Kmax), inferior-superior topography power difference (I - S), and higher-order aberration profile derived from wavefront analysis. RESULTS: Three patients are presented in this case series. Uncorrected visual acuity improved in all eyes by an average of 2.75 lines. Corrected visual acuity improved in 2 eyes and remained unchanged in 1 eye. Refractive astigmatism decreased in all patients by an average of 2.50 D. Kmax decreased by an average of 1.43 D. All patients had improvement in the I - S value with a mean decrease of 5.13 D. CONCLUSIONS: Topography-guided repositioning and/or replacement of corneal ring segments can result in improved topographic, optical, and visual outcomes in patients in whom the initial result is suboptimal. In these cases, a single segment repositioned beneath the cone resulted in an improved outcome. Analysis of corneal topography can guide the surgeon in treatment planning and can suggest patients in whom such an effort will be rewarded with better results.