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Use of retinal biopsy to diagnose Bartonella (formerly Rochalimaea) henselae retinitis in an HIV-infected patient.

A patient with the acquired immunodeficiency syndrome developed bilateral retinitis due to a Bartonella (formerly Rochalimaea) henselae infection. A retinal biopsy was performed when severe and progressive retinal infection failed to respond to empirical treatment for cytomegalovirus and Toxoplasma gondii. The biopsy specimen was stained with routine histopathological stains and the Steiner silver stain. Ribosomal DNA was extracted from formalinfixed, paraffin-embedded retinal tissue and amplified with the polymerase chain reaction assay, using Bartonella-specific primers. The amplified DNA fragment was cloned and sequenced. Staining with hematoxylin-eosin revealed tufts of proliferating vascular endothelium with numerous fusiformappearing cells, consistent with a diagnosis of bacillary angiomatosis. A Steiner silver stain revealed numerous small bacilli in the biopsy specimen. Amplification of DNA extracted from the tissue produced a fragment of 16S ribosomal DNA of the expected size; sequencing of the DNA fragment revealed that the infection was caused by B henselae. The retinal infection was treated with minocycline, doxycycline, and ciprofloxacin with improvement in visual acuity in the ensuing 12 weeks. To our knowledge, this is the first human immunodeficiency virus-infected patient with retinitis due to B henselae who was diagnosed by the identification of silver-staining bacilli and amplification and sequencing of B henselae with a polymerase chain reaction assay using a biopsy specimen of retinal tissue. Retinal biopsy is indicated, despite its potential for serious complications, in patients with acquired immunodeficiency syndrome who have a progressive, sight-threatening retinitis that is undiagnosed and unresponsive to therapy.

AIDS-Related Opportunistic Infections↗

Rhegmatogenous retinal detachment in angiomatosis retinae.

Three patients with von Hippel tumors of the retina developed rhegmatogenous retinal detachments caused by surface traction on the angioma. The break in each case was located at the posterior base of the angioma, between the afferent and efferent vessels. Conventional scleral buckling surgery with cryotherapy and a silicone episcleral sponge successfully reattached the retina in all three cases.

Adolescent↗

Cytomegalovirus infection in a healthy adult associated with recurrent branch retinal artery occlusion.

The authors report a 16-year-old healthy male who developed branch retinal artery occlusions sequentially in both eyes. A few vitreous cells and retinal vasculitis were associated findings. A complete work-up of the patient for an etiology for the occlusions failed to show any possible embolic source. Spinal fluid studies showed increased protein content and lymphocytic pleocytosis. Serologic studies showed a tenfold rise in the cytomegalovirus (CMV) titer. Other viral titers did not rise. CMV could not be cultured from the patient's body. The case represents a possible cause of the so-called idiopathic recurrent branch retinal artery occlusion syndrome.

Acute Disease↗

Unusual exudative retinal detachment 9 months after scleral buckling surgery.

A 49-year-old man developed exudative retinal detachment 9 months after uncomplicated scleral buckling surgery in the left eye. The subretinal exudates were strictly localized along the buckle and showed remarkable response to steroid. The cause would be noninfectious inflammation like posterior scleritis, triggered by the buckle itself or its associated factors. It is important to note that subretinal exudates long after scleral buckling can occur in consequence of steroid-responsive inflammation as well as insidious bacterial or fungal infection described previously.

Exudates and Transudates↗

Laser photocoagulation repair of recurrent macula-sparing retinal detachments.

Laser photocoagulation was performed around a detached retina in 4 patients who developed localized retinal detachment after successful scleral buckling. The range of retinal redetachment in all 4 patients was no larger than that of the initial retinal detachment and did not go over the vascular arcade. No evidence of vitreous traction or proliferative vitreoretinopathy was observed in these cases. Laser photocoagulation was performed in 3 lines of gray-white burn around the detached retina. Retinal attachment occurred between 4 and 14 days of laser treatment in all cases. No procedure related complications were seen. Laser photocoagulation may be an alternative procedure for the treatment of redetached retina with little and shallow detachment, before considering resurgery.

Adult↗

An ultrastructural study of nutritionally induced and reversed retinal degeneration in cats.

Kittens and adult cats fed a semipurified diet containing casein developed a retinal degeneration that initially involved photoreceptor outer segments in the area centralis. By electron microscopy, cone and rod outer segment lamellar discs could be seen to become vesiculated, frayed, disoriented and twisted. Shortening and subsequent disappearance of outer segments was followed by loss of photoreceptor nuclei, primarily in the area centralis but also in the midperipheral retina. The electroretinogram (ERG) indicated progressive reduction in cone and rod amplitudes and a delay in the temporal aspects of the cone response. When dietary casein was replaced by egg albumin in the diets of cats with minimal to moderately advanced degeneration, the degeneration was reversed; rod ERG function and structure returned essentially to normal, whereas some abnormalities of cone outer segment structure and a delay in the temporal aspects of the cone ERG persisted. The data provide strong evidence that dietary casein is a factor in this retinopathy and suggest that an alteration in protein metabolism of the photoreceptor may result from the dietary protein inadequacy.

Animals↗

Regulation of matrix metalloproteinase expression by tumor necrosis factor in a murine model of retinal neovascularization.

PURPOSE: Hypoxia and growth factors are postulated to be involved in the development of retinal neovascularization through the regulation of extracellular proteinase production. It has been shown that matrix metalloproteinases (MMPs) are elevated in the retina during the neovascularization process. However, the factors and mechanisms that regulate the expression of these enzymes are not well characterized. The present study examines the potential role of tumor necrosis factor (TNF)-alpha as a regulator of MMPs in the retinal neovascularization process. METHODS: C57/Bl6 mice were treated with 75% oxygen (experimental) or room air (control) from postnatal days (P)7 through P12, followed by room air until P17. Retinas were collected at P13, P15, or P17 and total RNA analyzed for the relative level of TNFalpha, TNF receptor (p55), and TNFalpha-converting enzyme (TACE). Immunostaining was used to identify changes in TNF protein expression as well as to localize TNFalpha within specific retinal cell types. The role of TNFalpha in stimulating retinal microvascular endothelial cell (RMVEC) proteinase production was evaluated using isolated murine RMVECs grown in normoxic or hypoxic conditions. Message expression was analyzed by RT-PCR and protein expression by zymographic analysis. RESULTS: TNFalpha mRNA was increased in the retinas of experimental animals on P13 and P15, during the early stages of retinal neovascularization. In addition to being expressed by Müller glial cells and the inner nuclear layer, additional expression was noted in the outer nuclear layer of experimental animals. No significant level of apoptosis was detected in the retina of experimental animals with retinal neovascularization. Isolated RMVECs did not significantly increase MMP production directly in response to a hypoxic stimulus, but required the presence of exogenous TNFalpha. TNFalpha increased the expression of MT1-MMP, MMP-3, and MMP-9 in these cells. The levels of TACE and p55, proteins important in mediating the response of cells to TNFalpha, were found to be increased by the angiogenic protein, vascular endothelial growth factor (VEGF), which was also elevated in the experimental retinas. CONCLUSIONS: TNFalpha levels increase in experimental mouse retinas exposed to hypoxic stimuli. Increased production of MMPs by RMVECs does not occur directly in response to a hypoxic stimulus. These cells are responsive, however, to stimulation by TNFalpha, which enhances the production of specific members of the MMP family. VEGF also plays a role in this process through its regulation of TACE and p55 mRNA in the vascular endothelial cells. These findings support the hypothesis that these two growth factors have a role in the regulation of extracellular proteinase expression during retinal neovascularization.

ADAM Proteins↗

Decreasing the risk of diabetic retinopathy in a study of case management: the California Medi-Cal Type 2 Diabetes Study.

OBJECTIVE: Diabetic retinopathy affects >60% of people with type 2 diabetes during the first 2 decades of the disease and is ameliorated by good glycemic control. This study tested whether intensive diabetes case management could prevent or delay diabetic retinopathy in patients with established type 2 diabetes. RESEARCH DESIGN AND METHODS: This study was part of a randomized, controlled clinical trial of diabetes case management in type 2 diabetes in southern California counties serving low income ethnic minority populations. Subjects were randomized to intervention (diabetes case management) or control (traditional treatment) groups. Subjects with at least two retinal photographs (n = 149) were included in this analysis to assess the effect of intervention on development or progression of diabetic retinopathy. RESULTS: Progression of retinopathy in the intervention group was not significantly less than in the control group (P = 0.226). However, those in the intervention group with no evidence of retinopathy at baseline were less likely to develop diabetic retinal changes (5/48) during a mean follow-up of 23.1 months than those in the control group (10/34, chi(2) = 4.805, P = 0.028). This difference remained significant in a logistic regression model that controlled for potential confounders (odds ratio 5.35 [95% CI 1.14-25.12]). CONCLUSIONS: This study shows that a relatively short duration of case management instituted before the onset of clinically identifiable retinopathy significantly diminished the risk of developing retinopathy in patients with type 2 diabetes. The findings also emphasized the retinal disease burden in this population, with development and progression of retinopathy occurring in <2 years.

Adult↗

Irradiation pretreatment before fibroblast implantation in experimental PVR.

Fibroblast injection into the vitreous body causes traction detachment in the rabbit's eye. Various working groups reported different results on the main causes of the development of experimental PVR. These contradictions encouraged us to investigate the main source of experimental PVR by irradiating the ocular tissues before fibroblast implantation thus suppressing cell proliferation originating from host tissue. Over a period of 3 weeks, 22 eyes received ten radiations in a total dosage of 3000 rad. After the last radiation, 250,000 fibroblasts were implanted into 22 eyes. In another 4 eyes, fibroblast implantation but no radiation was carried out. After 8 weeks, 59% of 22 eyes developed different stages of retinal detachment. Comparison with the group of unirradiated eyes, which developed retinal detachment in 85%, revealed no significant differences in the number of detachments.

Animals↗

Improvement in efficacy of corticosteroid therapy in an animal model of proliferative vitreoretinopathy by pretreatment.

Intraocular injection of the corticosteroid triamcinolone acetonide reduces the incidence of retinal detachment in rabbit eyes injected with tissue-cultured fibroblasts. When the steroid was injected simultaneously with the cells, a reduction of retinal detachment from 93% (control) to 75% (treated) was achieved on day 28. When the steroid was injected 24 h preceding cell injection, the reduction of retinal detachment was from 85% (control) to 43% (treated). The development of retinal detachment is caused by proliferation of injected fibroblasts. Reduction of this proliferation is probably achieved partially through direct inhibition of mitosis, but more important may be the reduction of the reactive inflammatory process.

Animals↗

Natural history of posterior vitreous detachment with early management as the premier line of defense against retinal detachment.

PURPOSE: This study was designed to elucidate various aspects of the natural history of posterior vitreous detachment (PVD), in particular the relation between symptomatology and prognosis as it relates to management of patients with the earliest symptoms of PVD. METHODS: A prospective study of 350 consecutive patients with PVD was performed, excluding all patients referred from an ophthalmologist, those with symptoms of more than 3 months in duration, and those with a history of ocular trauma, except for cataract surgery. Aphakia was present in 21 eyes, and 50 patients were bilaterally involved. RESULTS: Of 163 patients who had one to two floaters as their presenting symptom, with or without light flashes, a retinal tear developed in 12 (7.3%). Of 31 phakic eyes with secondary retinal tears on initial examination, 9 (29%) had one to two floaters and light flashes as the only symptoms. Of eight phakic eyes that initially, or eventually, had a retinal detachment, three (37%) had an interval of 2 1/2 to 3 weeks before visual field loss, during which they noticed only one to three visual floaters plus light flashes as their only symptoms. This early stage in which symptoms are detectable is crucial in terms of providing an opportunity for early treatment that might prevent retinal detachments. CONCLUSIONS: The prompt and conscientious vitreoretinal examination of each patient older than 45 years of age who experiences vitreous floaters, even though limited to one or two, should be undertaken without delay. This practice, combined with expeditious treatment of any secondary retinal tears, provides the most effective known means of preventing rhegmatogenous retinal detachment, and currently it appears to be neglected. A national public educational effort should be pursued to publicize the importance of these symptoms.

Adult↗

Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.

Adolescent↗

[Outer retinal edema or multifocal choroiditis after retinal detachment surgery. A case report].

CASE REPORT: We describe a case of a woman who, in the postoperative period of retinal detachment, developed an ophthalmoscopic picture which could correspond to abnormal outer retinal swelling or multifocal choroiditis. Ophthalmoscopic appearance consists of multiple yellowish subretinal lesions in the temporal area of the posterior pole with a cobblestone appearance. DISCUSSION: The two entities are extremely rare complications of rhegmatogenous retinal detachment surgery, with very similar funduscopic appearance. The first one consists of localized pockets of subretinal fluid remaining after retinal detachment surgery. Multifocal choroiditis is an inflammatory process related to various causes.

Choroiditis↗

Genetic predisposition to coronavirus-induced retinal disease.

PURPOSE: Retinal inflammatory and degenerative processes in humans and animals frequently are associated with genetic factors. The murine coronavirus, mouse hepatitis virus (MHV), JHM strain, induces a biphasic retinal disease in adult BALB/c mice. The genetic constitution of the host and the virus serotype can be critical factors in determining the outcome of a virus infection. The purpose of this study was to evaluate the possible role of host genetics in murine coronavirus-induced retinal disease. METHODS: JHM virus was inoculated by the intravitreal route into BALB/c, CD-1, and A/J mice. At varying times after inoculation, eye tissues were evaluated histologically. Antibody responses to the virus were evaluated by neutralization assays. RESULTS: JHM virus induces a biphasic retinal disease in BALB/c mice. In the early phase, 1 to 7 days after inoculation, retinal vasculitis is observed. The second phase, characterized by retinal degeneration in the absence of inflammation, is seen by day 10 and progresses for several months. There is a similar biphasic disease process in JHM virus-infected A/J mice. However, retinal changes are less severe than those seen in BALB/c mice. Retinal tissue damage induced by JHM virus in CD-1 mice is different. Only the early phase of the disease, consisting of retinal vasculitis, was observed. These CD-1 mice do not develop the retinal degenerative disease. In fact, after day 10, the retina has a normal appearance. These differences in retinal tissue damage are seen over a wide range of infectivity of the virus inocula. Virus concentrations ranging from 10(1.4) to 10(4.4) TCID50/5 microliters were capable of inducing both inflammation and degeneration in BALB/c mice, whereas, the highest concentration of virus (10(4.4) TCID50/5 microliters) in CD-1 mice resulted in only the early inflammatory changes. CONCLUSIONS: The authors show that the genetics of the host can profoundly affect the nature of retinal tissue damage. These studies substantiate the concept that a virus can indeed trigger retinal degenerative processes in genetically susceptible hosts.

Animals↗

Retinal arteriovenous anastomoses in the Vogt-Koyanagi-Harada syndrome.

A 15-year-old black girl had acute bilateral uveitis and other features of the Vogt-Koyanagi-Harada syndrome. Several months after the onset of her illness, she developed acquired retinal arteriovenous anastomoses in both eyes. By using fluorescein angiography, we documented that the anastomoses were collateral vessels developing in areas of damaged retinal pigment epithelium and retinal capillaries.

Adolescent↗

Postnatal development of photoreceptor proteins in mutant mice and Abyssinian cats with retinal degeneration.

Using immunocytochemical techniques, development of opsin, transducin alpha and S-antigen in photoreceptor cells of the mice homozygous or heterozygous for the rd or rds genes has been found to be similar to that of control animals during the first postnatal week. Even though the absolute amounts of these proteins are low (eg. opsin in the rds retina) or decrease in the postnatal period (as in the rd retina), we can demonstrate their persistence during the entire degeneration process. In fact, the content of the proteins in the photoreceptor perikarya actually appear to be higher after postnatal day 11 in all mutants studied. Thus, one of the major manifestations of the mutant retinae is a loss of polarity of the photoreceptor cells at the time of ROS degeneration without a loss in the ability to synthesize these important proteins of the visual cycle. This correlates well with the apparent defect in IRBP secretion and its intracellular accumulation in mutant photoreceptor cells as previously observed (van Veen et al. 1986). In the Abyssinian cat model for progressive retinal atrophy, the development an cellular distribution of all the proteins studied are similar in affected and control retinae until the beginning of stage 2 of the disease. At this time, outer segments begin to degenerate and immunoreactivity increases in the photoreceptor perikarya. The IRBP content of the retina declines markedly at stage 2, preceding extensive loss of photoreceptors.

Aging↗

Involution of threshold retinopathy of prematurity after diode laser photocoagulation.

OBJECTIVE: To characterize the process of involution of threshold retinopathy of prematurity after transpupillary diode laser photocoagulation. DESIGN: Retrospective case series. PARTICIPANTS: Neonates with threshold retinopathy who underwent diode laser photocoagulation of the peripheral avascular retina. METHODS: A retrospective chart review was done of the weekly examination records of infants treated for threshold disease. Features that were studied included the presence of residual stage 3 neovascularization, plus disease, and development of retinal detachment (RD). MAIN OUTCOME MEASURES: Timing of full involution and/or development of an RD. RESULTS: Of 262 eyes of 138 infants treated, full involution without RD was seen in 8%, 43%, 64%, 73%, and 86% of eyes at postoperative weeks 1, 2, 3, 4, and 9+/-3, respectively. Retinal detachments were diagnosed cumulatively in 0%, 1.5%, 4.2%, 6.5%, and 14% of eyes at weeks 1, 2, 3, 4, and 9+/-3, respectively. CONCLUSIONS: Full involution of laser-treated threshold retinopathy of prematurity required more than 2 weeks in more than half of treated eyes. Most RDs were not detected until > or =3 weeks after treatment.

Gestational Age↗

Mechanisms of retinotopic map development: Ephs, ephrins, and spontaneous correlated retinal activity.

This chapter summarizes mechanisms that control the development of retinotopic maps in the brain, focusing on work from our laboratory using as models the projection of retinal ganglion cells (RGCs) to the chick optic tectum (OT) or rodent superior colliculus (SC). The formation of a retinotopic map involves the establishment of an initial, very coarse map that subsequently undergoes large-scale remodeling to generate a refined map. All arbors are formed by interstitial branches that form in a topographically biased manner along RGC axons that overshoot their correct termination zone (TZ) along the anterior-posterior (A-P) axis of the OT/SC. The interstitial branches exhibit directed growth along the lateral-medial (L-M) axis of the OT/SC to position the branch at the topographically correct location, where it arborizes to form the TZ. EphA receptors and ephrin-A ligands control in part RGC axon mapping along the A-P axis by inhibiting branching and arborization posterior to the correct TZ. Ephrin-B1 acts bifunctionally through EphB forward signaling to direct branches along the L-M axis of the OT/SC to their topographically correct site. Computational modeling indicates that multiple graded activities are required along each axis to generate a retinotopic map, and makes several predictions, including: the progressive addition of ephrin-As within the OT/SC, due to its expression on RGC axon branches and arbors, is required to increase topographic specificity in branching and arborization as well as eliminate the initial axon overshoot, and that interactions amongst RGC axons that resemble correlated neural activity are required to drive retinotopic refinement. Analyses of mutant mice that lack early spontaneous retinal waves that correlate activity amongst neighboring RGCs, confirm this modeling prediction and show that correlated activity during an early brief critical period is required to drive the large-scale remodeling of the initially topographically coarse projection into a refined one. In summary, multiple graded guidance molecules, retinal waves and correlated spontaneous RGC activity cooperate to generate retinotopic maps.

Aging↗