Evolution of Keratoconus: From Diagnosis to Therapeutics.

This review describes the evolution of the diagnosis and treatment of keratoconus from the earliest written description to present day. The first description was provided in 1736 by Benedict Duddell who described the prominent corneas of a fourteen-year-old boy. Throughout the 19th century, a variety of surgical procedures were proposed to manage the disease, such as surgically repositioning the pupil away from the cone, iris incarceration to produce a slit-like pupil, cauterization of the cone to produce a scar, and full thickness elliptical excision of the cone. Despite the ingenuity of these procedures, many led to serious complications. In 1936, Ramon Castroviejo revolutionized surgical management by performing the first corneal transplant for keratoconus. The advent of refractive surgery in the 1990s brought about a sudden and critical need for better understanding of keratoconus and corneal ectatic disease. Topographic analysis allowed for earlier detection of keratoconus, prior to clinical signs and symptoms. Tomographic analysis provided analysis of the anterior and posterior surfaces of the cornea and allowed for even earlier detection. The Belin/Ambrosio Enhanced Ectasia Display on the Pentacam incorporates anterior and posterior elevation, pachymetric map, best fit sphere and enhanced reference surface to provide an overall "D" value that is predictive of ectatic disease. This display allows refractive providers to quickly and accurately screen potential refractive surgery candidates to identify those at risk for ectasia and early subclinical keratoconus. Corneal crosslinking was revolutionary in the treatment of keratoconus. There have been several randomized controlled trials that have found it to be safe and effective to halt ectatic progression. Crosslinking was recently approved by the FDA for progressive keratoconus. Currently, there is no clear definition of ectasia progression. Providers must be able to clearly, objectively and consistently diagnose progressive disease to institute timely treatment in the population with the greatest potential benefit. The new Belin ABCD grading system and progression analysis incorporated into the Oculus Pentacam software provides an objective way of assessing progression over time. Keratoconus diagnosis and management have grown tremendously since the first description in 1736, but there is still much to learn about keratoconus and its management.

Diagnostic and clinical characteristics of early-manifesting females with Duchenne or Becker muscular dystrophy.

Manifestations of Duchenne and Becker muscular dystrophy (DBMD) are present in up to 40% of heterozygous females, but there are few reports of females who exhibit skeletal muscle symptoms in childhood. From the Muscular Dystrophy Surveillance Tracking and Research Network, a multi-site population-based surveillance network for dystrophinopathy, nine symptomatic female heterozygotes with onset of symptoms prior to age 9 years were identified. The median age at diagnosis was 8.3 years, and the median interval from first symptoms to diagnosis was 1.35 years. Of the nine female heterozygotes, four had a positive family history, seven had intellectual disability and five had at least one mental health disorder. Mental health concerns included attention deficit hyperactivity disorder (ADHD), autism spectrum features, bipolar disorder, and depression. The frequency of intellectual and mental health problems in this group is higher than previously reported for affected males and for symptomatic females. These findings may have implications for diagnosis of early manifesting heterozygotes and for their health supervision.

Keratoconus and corneal morphology in patients with Down syndrome at a pediatric hospital.

PURPOSE: To evaluate patients with Down syndrome for keratoconus and corneal abnormalities using Scheimpflug imaging (Pentacam HR) in a pediatric setting. METHODS: The Pentacam scans of patients with Down syndrome seen at Children's Hospital Colorado Ophthalmology Department were reviewed retrospectively, and the following data were collected: keratometry values, pachymetry values, components of the Belin ABCD Grading System, the Belin/Ambrosio enhanced ectasia display D value, and topometric indices, including ISV, IVA, and KI. Subjective interpretation was used to classify scans as normal, abnormal, keratoconus suspect, and definite keratoconus. RESULTS: A total of 56 eyes of 31 patients aged 4-24 years (mean, 12.4) were included. The average value for K1 was 44.95 ± 1.73 D (range, 40.90-49.3 D); for K2, 46.87 ± 2.16 D (range, 42.50-51.80 D); for Kmax, 48.20 ± 3.11 D (range, 43-61.7 D); and for Kmean, 45.81 ± 1.85 D (range, 41.7-50.35 D). Mean pachymetry at the thinnest point was 509 ± 44.24 µm (range, 410-612 µm) and at the apex was 519 ± 44.24 µm (range, 412-646 µm). The mean D value was 2.08 ± 1.57 (range, 0.08-9.71). There were 10 patients (32%) with either keratoconus suspect or definite keratoconus in at least one eye. CONCLUSIONS: We found a high frequency of keratoconus and keratoconus suspect in pediatric and young adult patients with Down syndrome. The corneas in this population had steeper K values and thinner pachymetry values compared to previously reported controls.

Long-Term Tomographic Evaluation of Unilateral Keratoconus.

PURPOSE: To report 5 cases of advanced unilateral keratoconus documented by sequential tomographic evaluation. METHODS: Retrospective review over a 10-year period at a single practice identifying patients with unilateral keratoconus by advanced imaging throughout the follow-up period. RESULTS: Five patients were identified with progressive keratoconus in 1 eye and no changes in the fellow eye based on full tomographic evaluation and analysis of both anterior and posterior corneal surfaces and corneal thickness with a mean follow-up period of 59 months (range 39-86). CONCLUSIONS: Keratoconus is believed to be a bilateral disease that can present asymmetrically. We present 5 cases that appear to be true unilateral keratoconus with no associated mechanical environmental factors.

Incidence rate and occurrence of visually significant cataract formation and corneal decompensation after implantation of Verisyse/Artisan phakic intraocular lens.

PURPOSE: To evaluate the incidence rate and indications for explantation of Verisyse phakic intraocular lenses (pIOLs) over a 13.6 year period. SUBJECTS AND METHODS: Case series describing six cases of explantation of Verisyse pIOLs, out of 213 eyes with Verisyse pIOLs, implanted over a 13.6 year period by one surgeon at one institution, with mean follow-up of 5.6 years per eye. RESULTS: Four pIOLs were removed to facilitate extraction of a visually significant cataract, one was removed due to both cataract formation and development of corneal decompensation, and another was removed due to development of localized peripheral corneal decompensation. The incidence rate of pIOL removal was five per 1,000 patient-years with pIOL. Mean time from insertion of pIOL to cataract removal was 9.3 years (range 4.0-12.6 years). Mean time from insertion of pIOL to development of corneal decompensation was 10 years (range 6.9-13 years). There was no increase in the rate of cataract extraction in the pIOL population compared to the general population. CONCLUSION: Cataracts may develop in patients with pIOLs, necessitating removal of the pIOL. Corneal decompensation is a serious complication that appears to be directly related to pIOLs. Corneal decompensation can occur up to 13 years following implantation of pIOLs, and long-term follow-up is important to monitor for this complication.

In vitro pilot analysis of uniformity, circularity, and concentricity of DSAEK donor endothelial grafts prepared by a microkeratome.

PURPOSE: The aim of this study was to analyze Descemet stripping automated endothelial keratoplasty donor endothelial grafts, prepared by using a microkeratome, in terms of uniformity, circularity, and concentricity. METHODS: In this pilot study, 12 human donor corneas were prepared by means of a microkeratome and imaged using the Visante anterior segment optical coherence tomography along 4 meridians. The microkeratome enters and exits the corneal tissue at an angle, creating a donor graft bed with a uniform stromal (US) thickness in between the angled edges. We termed the angled portion the "nonuniform stromal transitional annulus" (STA), the point of entry and exit of the microkeratome the "epithelium-to-epithelium" (E-E) diameter, and the length of the US bed the "US" diameter. The E-E and US diameters were measured to create a model of each donor graft, from which circularity and concentricity were calculated. The STA length and height were measured, and the slope was calculated. RESULTS: The mean E-E diameter was 10.69 ± 0.32 mm (range, 9.46-11.75 mm) and the mean US diameter was 8.96 ± 0.40 mm (range, 7.62-10.28 mm). The microkeratome generated elliptical rather than circular cuts, with a mean eccentricity of 0.34 ± 0.098 (range, 0.22-0.58). Eccentricity values between 0 and 1 represent ellipses, with zero characterizing a circle. The US ellipses and E-E ellipses were not concentric, with a mean deviation of the centers of the shapes of 177.06 ± 92.06 µm (range, 21.95-322.22 µm). The mean STA length was 0.73 ± 0.31 mm (range, 0.25-1.89 mm), the mean height was 0.43 ± 0.08 mm (range, 0.28-0.64 mm), and the mean slope was 34.11 ± 14.00° (range, 8.43-53.67°). CONCLUSIONS: Microkeratome cuts created nonuniform, noncircular nonconcentric donor grafts. Asymmetry and nonuniformity of donor tissue may help explain suboptimal visual outcomes.