How a Devastating Case of Acanthamoeba Sclerokeratitis Ended up with Serious Systemic Sequelae.

A 35-year old soft contact lens wearer with a proven bilateral Acanthamoeba keratitis developed a nodular scleritis. Based on the stepladder approach described by Iovieno et al. [Ophthalmology. 2014 Dec;121(12):2340-7], nonsteroidal anti-inflammatory drugs, methylprednisolone, and later azathioprine were added to the antiamoebic treatment. Unfortunately, there was further deterioration and an endophthalmitis developed. Unbearable pain and concerns of spread to the brain urged an enucleation. Histopathological examination confirmed Acanthamoeba cysts in the cornea, sclera, retina, choroid, and vitreous body. As a side effect of the immunosuppressive treatment, the patient developed myopathy, pulmonary aspergillosis, and an avascular necrosis of the hip. Scleritis is a devastating complication of Acanthamoeba keratitis with a poor prognosis and a high enucleation rate. Acanthamoeba sclerokeratitis is, due to cyst-free biopsies, mostly assigned to an immune-mediated mechanism, justifying the use of immunosuppressive treatment. Scleritis in our case contributed to the extracorneal spread of Acanthamoeba. Our case is the first documented extracorneal spread of Acanthamoeba without previous surgery. Extracorneal spread of Acanthamoeba should be considered, even in the case of false-negative biopsies. We strongly recommend serial sections of the retrieved scleral specimen in case of negative histopathological examination to exclude an infection. Even when an immune-mediated scleritis is suspected, systemic immunosuppressive treatment should always be used with the greatest caution. Awareness of the side effects and monitoring by an experienced physician is mandatory.

Donor-Related Nontuberculous Mycobacterial Interface Infection After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To describe the first reported case of Mycobacterium chelonae-related interface keratitis after Descemet membrane endothelial keratoplasty (DMEK), successfully treated with DMEK exchange. METHODS: A case of donor-related DMEK interface keratitis, treated with medical therapy and DMEK exchange, was studied retrospectively. RESULTS: A patient with Fuchs endothelial dystrophy developed infectious interface keratitis after DMEK. In cultures of the donor cornea transport medium, M. chelonae was isolated. Subsequent clinical investigation showed early signs of infectious keratitis with multiple infiltrates at the donor-graft interface. Cultures at the cornea bank of origin also showed M. chelonae, indicating a donor-related infection. Because of unsuccessful medical therapy, the DMEK graft was exchanged 4.5 months after initial DMEK. After 2 weeks, some interface precipitates appeared. These precipitates regressed over the following months with continued medical therapy. Antibiotic therapy was successfully ended 5 months after DMEK exchange. CONCLUSION: This case highlights the importance of early diagnosis and intensive treatment of nontuberculous mycobacterial interface keratitis. If intensive medical therapy is able to contain infection but fails to eradicate interface keratitis, DMEK exchange is a possible treatment option.

Immunohistochemical Profiling of Corneas With Fuchs Endothelial Corneal Dystrophy.

PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is the leading indication for endothelial keratoplasty. Further insight into its pathophysiology is needed to develop alternative therapies. METHODS: Sixteen genes from a previous microarray expression experiment (FECD vs. normal) were validated using immunohistochemistry on paraffin-embedded corneas (n = 6 FECD, n = 6 normal). The results were quantified manually and semiautomatically. RESULTS: A higher percentage of corneal endothelial cells stained for alpha-smooth muscle actin (αSMA), cytokeratin 7, and superoxide dismutase 3 in FECD versus normal [odds ratios (ORs) of 60.90, 41.70, and 15.16, respectively, P < 0.001]. Dot-like staining for major histocompatibility complex, class II, DR alpha was present in FECD, but not in normal. Higher percentages of stromal cells in FECD versus normal stained for αSMA (OR = 864.26, P < 0.001), brain-derived neurotrophic factor (BDNF, OR = 6.34, P = 0.005), fibroblast growth factor 7 (FGF-7, OR = 2.76, P = 0.011), FGF-9 (OR = 5.97, P < 0.001), receptor FGFR-3 (OR = 13.90, P = < 0.001), and serum amyloid A1 (OR = 3.45, P = 0.023). Higher percentages of corneal epithelial cells stained for αSMA (OR = 2.20, P = 0.006) and BDNF (OR = 3.94, P < 0.001) in FECD versus normal. CONCLUSIONS: These results support a role for epithelial-mesenchymal transition (αSMA), oxidative stress (superoxide dismutase 3), and major histocompatibility complex, class II, DR alpha cells with dendritic morphology in the pathophysiology of FECD. Furthermore, corneal stromal cells express trophic molecules (BDNF and FGFs) and markers of chronic inflammation (serum amyloid A1) in FECD.

Identification of Circulating Fibrocytes and Dendritic Derivatives in Corneal Endothelium of Patients With Fuchs' Dystrophy.

Purpose: Fuchs' endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy. Methods: CE from patients with late-onset FECD was compared with that of normal controls using microarray expression analysis (n = 4 FECD, n = 4 normal), reverse transcriptase quantitative PCR (n = 9 FECD, n = 8 normal), and immunohistology (n = 55 FECD, n = 15 normal). Results: This led to the identification of circulating fibrocytes and their dendritic derivatives in all examined CE samples with FECD (in all clinical stages of symptomatic FECD and independent of prior cataract surgery). These cells were not present in normal CE. In this study we characterize their morphology, protein expression profile, number, and localization within the CE layer of patients with FECD. Conclusions: Circulating fibrocytes and their dendritic derivatives are a new aspect of FECD that deserves further investigation. Because they are known to cause fibrosis in a variety of organs, they may play a similar role in FECD and might be a valuable target for nonsurgical therapy.

Bilateral congenital cataract with suspected lens-induced granulomatous uveitis.

A healthy newborn baby girl presented with congenital bilateral cataract. Within a few days of presenting she also developed bilateral granulomatous uveitis, a condition generally linked in newborns to congenital infections, most frequently TORCHES syndrome (toxoplasmosis, rubella, cytomegalic inclusion disease, herpesvirus, including Epstein-Barr, syphilis). Extensive investigation did not reveal any underlying etiologic mechanism. Treatment with topical and systemic steroids did not improve the uveitis. However, bilateral lens extraction resulted in a quick resolution of the uveitis.