Oxidative stress and diabetic retinopathy: development and treatment.

Diabetic retinopathy (DR) is the most common microvascular complication in diabetic patients and one of the main causes of acquired blindness in the world. From the 90s until date, the incidence of this complication has increased. Reactive oxygen species (ROS) is a free radical with impaired electron that usually participates in the redox mechanisms of some body molecules such as enzymes, proteins, and so on. In normal biological conditions, ROS is maintained in equilibrium, however its overproduction can lead to biological process called oxidative stress and this is considered the main pathogenesis of DR. The retina is susceptible to ROS because of high-energy demands and exposure to light. When the balance is broken, ROS produces retinal cell injury by interacting with the cellular components. This article describes the possible role of oxidative stress in the development of DR and proposes some treatment options based on its stages. The review of the topic shows that blindness caused by DR can be avoided by early detection and timely treatment.

Clinicopathologic studies of age-related macular degeneration with classic subfoveal choroidal neovascularization treated with photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a relatively new modality that is currently under clinical and experimental evaluation for treatment of subfoveal choroidal neovascularization (CNV). The authors report the case of an 82-year-old woman who underwent verteporfin-mediated PDT for classic subfoveal CNV. Fluorescein angiography performed 2 weeks after treatment disclosed reduction of the initial area of neovascularization and leakage by approximately 60%. Three weeks after PDT, however, the area of leakage was almost the same size as that before treatment. The patient underwent submacular membranectomy almost 4 weeks after treatment. The authors describe the ultrastructural vascular changes after PDT and a clinicopathologic study of classic CNV. METHODS: The submacular membrane was studied by light and electron microscopy and immunohistochemical techniques. RESULTS: Ultrastructural examination of the peripheral vessels showed evidence of endothelial cell degeneration with platelet aggregation and thrombus formation. Occasional occluded vessels were surrounded by macrophages, a phenomenon previously reported to describe the process of resorption of such blood vessels. The vessels in the center of the membrane were unremarkable. CONCLUSION: Photodynamic therapy causes endothelial cell damage, thrombus formation, and vascular occlusion of classic CNV in age-related macular degeneration.

Clinicopathologic correlation of an untreated macular hole and a macular hole treated by vitrectomy, transforming growth factor-beta 2, and gas tamponade.

PURPOSE: To study the clinicopathologic features of an untreated macular hole in the right eye and a macular hole in the left eye treated by vitrectomy, application of transforming growth factor-beta 2, and gas tamponade. METHODS: The patient, a 73-year-old man with bilateral macular holes, was studied clinically before and after surgical treatment of the macular hole in his left eye. The patient's eyes were obtained postmortem and serially step-sectioned through the macula and optic nerve head for electron microscopy. RESULTS: Examination of 1-micron thick plastic-embedded sections through the macula of the right eye disclosed a 0.6-mm macular hole with rounded gliotic margins, a thin epiretinal membrane, and parafoveal cystic changes. Examination of 1-micron thick plastic-embedded sections through the macula of the left eye disclosed a 0.25-mm defect in the fovea, which was bridged by glial cells. The glial cells were continuous with a thin hypocellular epiretinal membrane without contraction features on both sides of the defect. The ultrastructural features of the glial cells were consistent with Mueller cells. CONCLUSIONS: Treatment of a macular hole with vitrectomy, transforming growth factor-beta 2, and gas tamponade was followed by complete closure of the macular hole by Mueller cell proliferation.

Clinicopathologic correlation of an epiretinal membrane associated with a recurrent macular hole.

PURPOSE: To describe the clinicopathologic features of an epiretinal membrane associated with a recurrent, full-thickness idiopathic macular hole and speculate on the mechanism(s) contributing to its recurrence 1 year after initially successful closure of pars plana vitrectomy and gas tamponade (SF6). METHODS: After fixation of the 2 x 1 mm specimen in a mixture of 1% glutaraldehyde and 4% formaldehyde followed by 2.5% glutaraldehyde, postfixation with osmium tetroxide, and standard dehydration, the specimen was embedded in epoxy resin. Ultrathin sections were stained with uranyl acetate and lead citrate for transmission electron microscopy. RESULTS: Ultrastructural examination disclosed a fibrocellular membrane composed of Müller cells and fibrous astrocytes. Native collagen was entrapped in the matrix in some areas. CONCLUSION: Those cells that may lead to the closure of an idiopathic macular hole may also contribute to its recurrence if the reparative process goes awry.

Reassembly of corneal epithelial adhesion structures after excimer laser keratectomy in humans.

OBJECTIVE: To determine the pattern of long-term reformation of the adhesion structures after excimer laser phototherapeutic keratectomy. METHODS: Four corneal buttons were removed at penetrating keratoplasty 6 to 15 months after initial excimer laser phototherapeutic keratectomy. Morphometric analysis of electron micrographs of the wound bed was performed to determine the extent and pattern of reformation of hemidesmosomes, anchoring fibrils, and basal laminae. RESULTS: Eight percent of the basal epithelial cells had underlying normal anchoring fibrils at 6 months, compared with 35% at 15 months. The percentage of basal cell membrane occupied by hemidesmosomes remained fairly constant (35.2% to 37.7%). With the exception of a localized area of multilamination seen at 9 months, the cross-sectional area of basal lamina per 100 microns of basal cell membrane increased with the duration of wound healing (18.0 microns 2 at 6 months, 24.4 microns 2 at 15 months) but remained below normal levels (32 microns 2). CONCLUSIONS: These data suggest that after human excimer keratectomy, the anchoring fibrils and basal lamina do not completely normalize even after 15 months.

Secondary epiretinal membrane after blunt trauma.

Electron microscopic study of a surgically removed epiretinal membrane secondary to blunt trauma disclosed the membrane to be hypocellular and lined by internal limiting membrane on the external surface and by a layer of fibrocytes and myofibrocytes on the internal surface. The membrane was composed predominantly of new collagen. Occasional fibrous astrocytes, rare macrophages, and no blood vessels were present.

Clinicopathologic correlation of a macular hole treated by cortical vitreous peeling and gas tamponade.

PURPOSE: To study the histopathology of a stage III macular hole that had been treated by vitrectomy with cortical vitreous and epicortical vitreous membrane peeling and gas tamponade. METHODS: The light and electron microscopic features of a treated macular hole were studied. RESULTS: A 16-microns-wide break was present in the external limiting membrane. This was sealed by Müller cell processes. Photoreceptors adjacent to the healed defect appeared normal. No cystoid macular edema was present. CONCLUSION: Cortical vitreous peeling and gas tamponade can allow the macular hole to settle and the edges to re-approximate. The residual defect can be sealed by Müller cells.

Clinicopathologic correlation of choroidal neovascularization demonstrated by indocyanine green angiography in a patient with retention of good vision for almost four years.

OBJECTIVE: The clinicopathologic features of age-related macular degeneration (AMD) with occult choroidal neovascularization (CNV) detected by digital indocyanine green (ICG) videoangiography in an 82-year-old woman are discussed. METHODS: Serial sections through the macula of both eyes were prepared, and two-dimensional reconstruction maps depicting the histopathologic features were drawn. A technique by which electron microscopic examination of sections removed from glass slides was performed is described. RESULTS: Histopathologic examination of the lesion disclosed a 3.5 mm x 0.02 mm thick fibrovascular subretinal pigment epithelial choroidal neovascular membrane in an eye with diffuse basal laminar deposit in the macula. CONCLUSION: This case represents the first clinicopathologic correlation involving ICG videoangiography of CNV. The findings support the growing clinical impression that ICG videoangiography is of value in identifying what has been previously described as ill-defined or occult CNV.

Intraocular cilia. Report of six cases of 6 weeks' to 32 years' duration.

In this study, we describe the clinicopathologic features seen in six cases of intraocular cilia and review the features of previously reported cases. Ultrastructural studies of the cilia showed partial loss of the cuticle layer, diffuse accumulation of small electron-dense granules in cuticle and cortical cells, and loss of continuous cell membranes of the cortex. The cilia were almost completely intact in most of our cases. Intraocular cilia can be tolerated for long periods.

Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes.

Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns-Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles).

Intraocular gnathostomiasis.

The clinical and histologic features of an intraocular parasite from a 29-year-old woman are reported. The live organism was located in the posterior vitreous near the optic disc and was successfully removed by vitreous aspiration. The parasite was identified as an advanced stage larvae of Gnathostoma spinigerum. This is the first case report of the scanning electron microscopic findings of intraocular gnathostomiasis. The features of nine previously reported cases of intraocular gnathostomiasis are reviewed.

Clinicopathologic study of bilateral macular holes treated with pars plana vitrectomy and gas tamponade.

The clinicopathologic findings of light and electron microscopic examination of a 78-year-old woman who underwent successful bilateral pars plana vitrectomy for bilateral stage III macular holes are reported. Examination disclosed anatomical repair of the full-thickness macular holes by glial cell proliferation in the left eye. The hole apparently collapsed with no glial cell proliferation in the right eye. The photoreceptors adjacent to the healed macular holes appeared normal. Defects in the internal limiting membrane in the foveal area were noted in both eyes.

Modulation of corneal wound healing after excimer laser keratomileusis using topical mitomycin C and steroids.

A 193-nm excimer laser system was used to create deep stromal ablations in seven New Zealand white rabbits and shallow ablations in three. Eyes were randomized for treatment with topical mitomycin C, steroids, and erythromycin; topical steroids and erythromycin; or topical erythromycin only. All treatment regimens were instituted twice daily for 14 days. All eyes reepithelialized normally within 3 to 5 days. During 10 weeks of follow-up, all eyes developed moderate reticular subepithelial haze without significant differences among treatment groups. Results of light, fluorescence, and electron microscopic examination showed anterior stromal scarring and markedly reduced new subepithelial collagen formation in the group treated with mitomycin C, corticosteroids, and erythromycin. Focal abnormalities of Descemet's membrane and endothelial abnormalities were present in all treatment groups. Combination therapy with topical steroids, mitomycin C, and erythromycin to control the corneal wound healing response after refractive laser surgery appears promising and warrants further study.

A clinicopathologic study of the eyes in familial adenomatous polyposis with extracolonic manifestations (Gardner's syndrome).

The eyes of a 51-year-old woman with familial adenomatous polyposis and extracolonic manifestations (Gardner's syndrome) were obtained postmortem and studied by light microscopy and by transmission and scanning electron microscopy. We found a generalized abnormality in melanogenesis of the retinal pigment epithelium and at least three types of pigmented lesions. The histologic findings in one type of lesion were consistent with congenital hypertrophy of the retinal pigment epithelium or benign pigmented nevus of the retinal pigment epithelium. The other two types of lesion were most consistent with hamartomatous malformations of the retinal pigment epithelium featuring cellular hypertrophy, hyperplasia, and rarely retinal invasion and formation of a minute mushroom-shaped tumor. These histopathologic findings indicate a generalized effect of the familial adenomatous polyposis gene on the retinal pigment epithelium. This oncogene, which is responsible for tumor formation in the gastrointestinal tract, soft tissues, bone, and other locations in patients with familial adenomatous polyposis, also leads to a generalized defect in melanogenesis and focal lesions of the retinal pigment epithelium.

Autosomal-dominant fundus flavimaculatus. Clinicopathologic correlation.

The authors report the first clinicopathologic study of autosomal-dominant fundus flavimaculatus with late-onset atrophic macular degeneration in a 62-year-old man. Results of histopathologic examination disclosed the retinal pigment epithelium (RPE) to be distended by a periodic acid-Schiff (PAS)-positive, acid mucopolysaccharide-negative material. Transmission electron microscopy showed marked accumulation of lipofuscin and melanolipofuscin granules within the RPE. The different modes of genetic transmission and ultrastructural heterogeneity suggest that fundus flavimaculatus is a clinical syndrome representing several genetically and mechanistically distinct disorders whose common end-stage is a topographically similar accumulation of lipofuscin.

Clinicopathologic correlation of recurrent epiretinal membranes after previous surgical removal.

Recurrent epiretinal membranes (ERMs) causing macular pucker developed after surgical removal in seven eyes and were subsequently removed. A specimen was available for electron microscopic study from four of the seven primary operations and all seven of the repeat operations. The diagnostic associations for the primary cases included retinal holes or tears (four eyes), trauma, inflammation (one eye each). In one eye the membrane was idiopathic. The primary and recurrent ERM specimens contained similar cell types and structural characteristics but were not identical. No one cell type predominated in either primary or recurrent ERM. Compared with studies of idiopathic ERMs, myofibroblasts were present with increased frequency in recurrent membranes. Fibrocytes, fibrous astrocytes, and retinal pigment epithelial cells were also present in most specimens. Other features of both the primary and recurrent ERM specimens included the presence of cells with myoblastic differentiation, fragments of internal limiting membrane, new collagen, and nerve fiber elements.