Purpose
To analyze mitochondrial DNA (mt DNA) gene mutations in a 19-year-old female patient, who presented with chronic progressive external ophthalmoplegia (CPEO), together with her mother and younger sister.
Methods
The diagnosis of mitochondrial myopathy was made based on clinical and biologic analysis. Histochemical methods were used to detect ragged-red fibers (RRFs) and ragged-blue fibers (RBFs) on a muscle biopsy of the patient. All mitochondrial gene DNA fragments of the patient, her mother, and younger sister were amplified by polymerase chain reaction. The products were sequenced and compared with reference databases.
Results
A novel T1658C mutation and a known A10006G mutation were identified in the mitochondrial tRNAVal gene and the tRNAGly gene, respectively, in the patient, her mother, and younger sister. The T1658C mutation changes the T loop structure of mitochondrial tRNAVal and the A10006G mutation disturbs the D loop of mitochondrial tRNAGly.
Conclusions
The T1658C and A10006G mutations of mtDNA may be responsible for the pathogenesis of the patient with CPEO.
Corneal collagen crosslinking with riboflavin photosensitization and ultraviolet irradiation is a novel approach to limiting the progression of keratoconus in patients by increasing the elastic modulus of the degenerate cornea. Beneficial reductions in corneal steepness and aberrations after crosslinking also frequently occur. In a previous study, we described a computational modeling approach to simulating topographic progression in keratoconus and regression of disease with corneal collagen crosslinking. In the current study, this model has been expanded and applied to the inverse problem of estimating longitudinal time-dependent changes in the corneal elastic modulus after crosslinking using invivo measurements from 16 human eyes. Topography measured before crosslinking was used to construct a patient-specific finite element model with assumed hyperelastic properties. Then the properties of the cornea were altered using an inverse optimization method to minimize the difference between the model-predicted and invivo corneal shape after crosslinking. Effects of assumptions regarding sclera-to-cornea elastic modulus ratio and spatial attenuation of treatment effect due to ultraviolet beam characteristics on the predicted change in elastic modulus were also investigated. Corneal property changes computed by inverse finite element analysis provided excellent geometric agreement with clinical topography measurements in patient eyes post-crosslinking. Over all post-treatment time points, the estimated increase in corneal elastic modulus was 110.8±48.1%, and slightly less stiffening was required to produce the same amount of corneal topographic regression of disease when the sclera-to-cornea modulus ratio was increased. Including the effect of beam attenuation resulted in greater estimates of stiffening in the anterior cornea. Corneal shape responses to crosslinking varied considerably and emphasize the importance of a patient-specific approach.
A 47-year-old woman required penetrating keratoplasty in the right eye after developing delayed visually significant corneal scarring bilaterally after laser in situ keratomileusis (LASIK) in 1997 following epikeratoplasty in 1987. Spectral domain ocular coherence tomography of the left cornea showed a 100 μm lenticule with a LASIK flap posterior to the host Bowman layer at 250 μm. Histopathology and electron microscopy of the right corneal button showed a 120 μm lenticule with a LASIK flap within the lenticule at 100 μm. Clinically significant scarring was present within the LASIK flap interface, within the lenticule stroma, and within the area of the underlying host Bowman layer. There were keratocytes at the junction between the LASIK flap and lenticule stromal bed. Although epikeratoplasty is no longer practiced, post-epikeratoplasty patients may present for refractive surgical options and LASIK carries significant risks for corneal scarring in these individuals, especially when using flap-creating devices that may create thin LASIK flaps.
A 43-question survey was e-mailed to all resident members of the American Society of Cataract and Refractive Surgery (ASCRS), ASCRS members in practice for 5 or fewer years, and residency program directors of 118 U.S. Accreditation Council for Graduate Medical Education-accredited ophthalmology programs (for distribution to their residents) in June 2010. Two hundred eighty-five of 2279 surveys sent were completed and returned, for a response rate of 12.5%. Most respondents (88.7%) had served as primary surgeon in more than 100 cataract surgeries. Fifty-two percent of respondents had not performed corneal relaxing incisions; 60% had no experience implanting a toric IOL. Twenty-two percent had experience implanting a presbyopia-correcting IOL. Over 75% had not performed any corneal refractive surgical procedures. Although basic cataract case numbers appear adequate, there are significant perceived deficiencies in current resident training models for surgical astigmatism management, implanting presbyopia-correcting IOLs, and corneal refractive surgery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.
Purpose: The purpose of this study is to report a case of microsporidial endophthalmitis after penetrating keratoplasty in a healthy patient and discuss the management.
Methods: This is a case report.
Results: A 69-year-old healthy male underwent penetrating keratoplasty for corneal scar secondary to herpes stromal keratitis. He presented with features of acute graft rejection 3 years later. After failure of medical management, a repeat full thickness keratoplasty was performed. Pathologic examination of the corneal specimen showed microsporidia. The patient then developed a chronic endophthalmitis, and a vitreous tap and injection followed by pars plana vitrectomy were performed. Pathologic examination of tissue showed microsporidia.
Conclusions: Microsporidia are being increasingly identified as the cause of stromal keratitis. This is the first report of microsporidial endophthalmitis in a patient without underlying systemic illness.
We read with the interest the article by Cao et al. reporting spectacle wear adherence in aphakic children after bilateral cataract surgery. In their series, spectacle adherence was only 31% during the first year of life. Poor spectacle adherence during these formative years when central visual pathways are developing puts these children at risk for life-long visual disability. In contrast, contact lens adherence was much higher during the first year of life among participants in the Infant Aphakia Treatment Study (IATS) a multicenter, longitudinal, randomized clinical trial in the United States, which randomized infants after unilateral cataract surgery to primary intraocular lens (IOL) implantation or aphakia.
When individuals with central vision loss due to macular degeneration (MD) view stimuli in the periphery, most of them activate the region of retinotopic cortex normally activated only by foveal stimuli – a process often referred to as ‘reorganization’. Why do some show this reorganization of visual processing whereas others do not? We reported previously that six individuals with complete bilateral loss of central vision showed such reorganization, while two with bilateral central vision loss but with foveal sparing did not, and we hypothesized that the effect occurs only after complete bilateral loss of foveal vision. Here we conduct a stronger test of the dependence of reorganization of visual processing in MD on complete loss of foveal function, by bringing back one (called MD6) of the two participants who previously did not show reorganization, and who showed foveal sparing. MD6 has now lost all foveal function, and we predicted that if large-scale reorganization of visual processing in MD individuals depends on complete loss of foveal input, then we will now see such reorganization in this individual.
Interleukin-17 (IL-17), a pro-inflammatory cytokine produced by CD4+ Th17 cells, has been associated with the pathogenesis of several autoimmune diseases including uveitis. The fate of IL-17 during HIV/AIDS, however, remains unclear, and a possible role for IL-17 in the pathogenesis of AIDS-related diseases has not been investigated. Toward these ends, we performed studies using a well-established animal model of experimental murine cytomegalovirus (MCMV) retinitis that develops in C57/BL6 mice with retrovirus-induced immunosuppression (MAIDS). After establishing baseline levels for IL-17 production in whole splenic cells of healthy mice, we observed a significant increase in IL-17 mRNA levels in whole splenic cells of mice with MAIDS of 4-weeks (MAIDS-4), 8-weeks (MAIDS-8), and 10-weeks (MAIDS-10) duration. In contrast, enriched populations of splenic CD4+ T cells, splenic macrophages, and splenic neutrophils exhibited a reproducible decrease in levels of IL-17 mRNA during MAIDS progression. To explore a possible role for IL-17 during the pathogenesis of MAIDS-related MCMV retinitis, we first demonstrated constitutive IL-17 expression in retinal photoreceptor cells of uninfected eyes of healthy mice. Subsequent studies, however, revealed a significant decrease in intraocular levels of IL-17 mRNA and protein in MCMV-infected eyes of MAIDS-10 mice during retinitis development. That MCMV infection might cause a remarkable downregulation of IL-17 production was supported further by the finding that systemic MCMV infection of healthy, MAIDS-4, or MAIDS-10 mice also significantly decreased IL-17 mRNA production by splenic CD4+ T cells. Based on additional studies using IL-10 -/- mice infected systemically with MCMV and IL-10 -/- mice with MAIDS infected intraocularly with MCMV, we propose that MCMV infection downregulates IL-17 production via stimulation of suppressor of cytokine signaling (SOCS)-3 and interleukin-10.
Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomegalovirus, can manipulate expression of these host proteins, with overstimulation of SOCS1 and/or SOCS3 putatively facilitating viral evasion of immune surveillance, and SOCS suppression generally exacerbating immunopathogenesis. This is particularly poignant within the eye, which contains a diverse assortment of specialized cell types working together in a tightly controlled microenvironment of immune privilege. When the immune privilege of the ocular compartment fails, inflammation causing severe immunopathogenesis and permanent, sight-threatening damage may occur, as in the case of AIDS-related human cytomegalovirus (HCMV) retinitis. Herein we review how SOCS1 and SOCS3 impact the virologic, immunologic, and/or pathologic outcomes of herpesvirus infection with particular emphasis on retinitis caused by HCMV or its mouse model experimental counterpart, murine cytomegalovirus (MCMV). The accumulated data suggests that SOCS1 and/or SOCS3 can differentially affect the severity of viral diseases in a highly cell-type-specific manner, reflecting the diversity and complexity of herpesvirus infection and the ocular compartment.