Microsporidial Stromal Keratitis: Epidemiological Features, Slit-Lamp Biomicroscopic Characteristics, and Therapy.

PURPOSE: Microsporidial stromal keratitis is a rare form of infectious keratitis, with only 7 cases reported in the United States to date. This study was performed to evaluate risk factors, clinical features, and response to therapy. METHODS: A retrospective review of the medical records of all patients diagnosed with microsporidial stromal keratitis seen in the practices of the authors between 1999 and 2020 was performed. Diagnosis was determined by cytology or histopathology in corneal specimens. Risk factors, presence or absence of distinctive clinical features, and response to medical and surgical therapies were recorded. RESULTS: Nine patients-7M:2F, aged 7 to 99 years-with microsporidial stromal keratitis were identified. Exposures to recreational water and hymenopteran insect bites, both epidemiologically linked risk factors for systemic microsporidial infection, were identified in our patients. Presence of stromal edema with features of disciform keratitis and a distinctive granular keratitis were observed in 6 of 9 and 5 of 9 patients, respectively. Poor response to medical therapy was noted. Penetrating keratoplasty was effective in curing the infection. Final visual acuity was 20/40 or better in 6 of 9 patients. CONCLUSIONS: In patients with slowly progressive keratitis, history of exposure to recreational water or hymenopteran insects should be sought. In patients with corneal edema consistent with disciform keratitis, with evolution to a granular keratitis, microsporidia should be considered in the differential diagnosis. In cases of established microsporidial stromal keratitis, penetrating keratoplasty should be considered if prompt response to medical therapy is not noted.

Lamellar changes in the keratoconic cornea.

PURPOSE: The purpose of this study was to identify ultrastructural changes associated with ectasia and to determine the association between lamellar count and corneal thinning. METHODS: Five surgically removed keratoconic corneal buttons and four, non-keratoconic, normal eye bank control corneas were processed for transmission electron microscopy using an established protocol, ensuring minimal tissue distortion. A sequence of overlapping digital images, spanning the full apical cone corneal thickness, was assembled. A seamless digital montage was printed at 5000× magnification. Lamellae were counted in the anterior-posterior orientation, along a linear line, using established criteria for identification of individual lamellae. RESULTS: The stromal thickness estimated as a 95% confidence interval for the mean, CI (0.95), in the keratoconic corneas was 372 ± 62 µm, while in the normal cornea, it was 446 ± 89 µm. All keratoconic corneas showed ultrastructural evidence of lamellar splitting and a loss of interweaving anterior lamellae. In the keratoconic corneas, the median total linear stromal lamellar absolute count tangential to the corneal surface was 362, (25th percentile; 75th percentile) = (355; 365) lamellae and in the normal cornea, 246, (25th percentile; 75th percentile) = (239; 251). The linear lamellar density in the keratoconic corneas was estimated as CI (0.95) 117 ± 22 and 86 ±19 lamellae per 100 µm in the anterior and posterior portion of the stroma, respectively. In normal cornea, the linear lamellar density was estimated as CI (0.95) 51 ± 8 and 80 ± 20 lamellae per 100 µm. The mean difference of linear lamellar count between the anterior and the posterior portion of the cornea was estimated as CI (0.95) 31 ± 23 for keratoconic corneas and -29 ± 28 for the normal corneas. CONCLUSIONS: The current morphometric analysis of ultrastructural changes suggests that ectasia and thinning in keratoconus is associated with lamellar splitting into multiple bundles of collagen fibrils and loss of anterior lamellae. These structural changes, possibly in addition to lateral shifting of lamellae due to the pressure gradient over the cornea, are a potential explanation to the central loss of mass.

Recurrence or re-emergence of keratoconus--what is the evidence telling us? Literature review and two case reports.

Keratoconus may recur following penetrating or lamellar keratoplasty, but latency is considerably longer in the former. Since keratoplasty involves only partial excision of the cornea, and recent research strongly indicates the presence of the pathology in the peripheral host cornea, the reappearance of the pathology after a latency period is most likely due to migration of the disease from host to donor cornea. This notion is further corroborated by the shorter latency period in partial thickness keratoplasty, where more of the diseased host cornea remains in place. Other proposed causes for the recurrence of keratoconus, such as eye rubbing and contact lens wear, were reportedly not associated with a significant number of cases, and, therefore, are not the primary factor. Based on existing literature, it is concluded that, in post-keratoplasty keratoconus, the etiology stems from re-emergence of the disease rather than recurrence. Keratoconus patients in need of keratoplasty should be counseled on the possibility of the disease re-emerging.

Quantified histopathology of the keratoconic cornea.

PURPOSE: This study systematically investigated and quantified histopathological changes in a series of keratoconic (Kc) corneas using a physiologically formulated fixative to not further distort the already distorted diseased corneas. METHODS: Twelve surgically removed Kc corneal buttons were immediately preserved and processed for light and transmission electron microscopy using an established corneal protocol. Measurements were taken from the central cone and peripheral regions of the host button. The sample size examined ranged in length from 390 to 2608 µm centrally and 439 to 2242 µm peripherally. RESULTS: The average corneal thickness was 437 µm centrally and 559 µm peripherally. Epithelial thickness varied centrally from 14 to 92 µm and peripherally from 30 to 91 µm. A marked thickening of the epithelial basement membrane was noted in 58% of corneas. Centrally, anterior limiting lamina (ALL) was thinned or lost over 60% of the area examined, whereas peripheral cornea was also affected but to a lesser extent. Histopathologically, posterior cornea remained undisturbed by the disease. Anteriorly in the stroma, an increased number of cells and tissue debris were encountered, and some of these cells were clearly not keratocytes. CONCLUSIONS: It is concluded that Kc pathology, at least initially, has a distinct anterior focus involving the epithelium, ALL, and anterior stroma. The epithelium had lost its cellular uniformity and was compromised by the loss or damage to the ALL. The activity of the hitherto unreported recruited stromal cells may be to break down and remove ALL and anterior stromal lamellae, leading to the overall thinning that accompanies this disease.