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Optical coherence tomographic features of idiopathic submacular choroidal neovascularization.

PURPOSE: To clarify the morphologic features of idiopathic submacular choroidal neovascularization using optical coherence tomography. METHODS: Using optical coherence tomography, we prospectively examined 17 consecutive eyes (17 patients; eight men, nine women; mean age +/- SD, 36.0 +/- 9.3 years) with idiopathic submacular choroidal neovascularization. During the follow-up period (mean +/- SD, 7.5 +/- 3.8 months), we repeated optical coherence tomography in 15 eyes; optical coherence tomography was performed only at the initial examination in two eyes that underwent submacular surgery. RESULTS: Choroidal neovascularization was observed in the subsensory retinal space anterior to the retinal pigment epithelium as a highly or moderately reflective mass, which protruded from the retinal pigment epithelium in 13 of 17 eyes (protruding type). In four eyes, choroidal neovascularization was a highly reflective fusiform mass at the level of the retinal pigment epithelium and choriocapillaris (fusiform type). During the follow-up period, choroidal neovascularization regressed and the protruding mass became a highly reflective fusiform mass in 10 of 11 eyes with the protruding type that underwent repeated examination. In three of the 10 eyes, during 5 to 10 months from initial examination, the choroidal neovascularization was exacerbated and it again protruded into the subsensory retinal space anterior to the retinal pigment epithelium. Four eyes with the fusiform type remained the same throughout the follow-up period. The overlying retina was thickened and had low reflectivity in all 17 eyes at the initial examination. Optical coherence tomography identified subretinal fluid in only 11 of the 13 eyes with protruding type choroidal neovascularization. CONCLUSIONS: Optical coherence tomography confirmed subsensory retinal location of idiopathic submacular choroidal neovascularization anterior to the retinal pigment epithelium. Protruding choroidal neovascularization transforms to fusiform tissue at the level of the retinal pigment epithelium during the process of regression. Sensory retinal edema was always associated with choroidal neovascularization.

Adult↗

Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy.

OBJECTIVE: To determine the molecular basis of a retinopathy previously described as dominant macular subretinal neovascularization with peripheral retinal degeneration. METHODS: The TIMP3 gene was analyzed in family members, and 4 mutation-positive patients were studied using psychophysics and electroretinography. RESULTS: Cosegregating with disease in the family was a single base pair change in the TIMP3 gene, altering a conserved tyrosine to cysteine at amino acid position 172 (Y172C). There was psychophysical and electroretinographic evidence of rod dysfunction greater than cone dysfunction. Dark adaptometry showed abnormalities with regional retinal variation in degree. CONCLUSIONS: The Y172C mutation in the TIMP3 gene is another cause of Sorsby fundus dystrophy. The expression of this form of the disease, as in other C-terminal TIMP3 mutations, is speculated to be secondary to mutant TIMP-3, causing a decreased turnover of the extracellular matrix. CLINICAL RELEVANCE: The molecular clarification of inherited retinal degeneration involving abnormal extracellular matrix turnover in and around Bruch's membrane should provide clues to the pathogenesis of not only these particular diseases but also forms of age-related macular degeneration.

Adolescent↗

Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes.

Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression.

Adult↗

Repair of nasal fistula secondary to radiation therapy for Eales's disease.

Eales's disease is characterized by neovascularization and idiopathic retinal and vitreous hemorrhages. Therapy in the past included the use of radiation. A case is reported of a patient who received a dose of 15,000 roentgens (approximately 14,250 rad) to the right eye via temporal and nasal portals. He subsequently lost vision in that eye. Thirty years after the radiation was administered, a nasocutaneous fistula developed, and it was closed with a forehead island flap.

Eye Diseases↗

Classification and treatment of diabetic retinopathy.

Diabetic retinopathy is the leading cause of blindness. In Japan about 45% of diabetic patients under medical care have retinopathy and 10% have proliferative retinopathy. Until recently, Scott's classification (1953, 1957) of retinopathy was commonly used in Japan. As there are several problems with this classification, I proposed a new classification in 1983. It aims to separate benign and malignant types and to be more useful clinically so that each stage corresponds better to the indication of specific treatment. Diabetic retinopathy is divided into benign (type A) and malignant (type B) retinopathy, and each type is subdivided into 5 stages. Benign retinopathy is unlikely to cause blindness unless maculopathy is present. It includes background retinopathy (A1 and A2) and interrupted proliferative retinopathy (A3, A4 and A5) after photocoagulation or vitrectomy. Malignant retinopathy is likely to get worse and may lead to blindness if left without specific treatment. It includes preproliferative retinopathy (B1), early (B2), advanced (B3) and end-stage (B4 and B5) proliferative retinopathy. The presence of specific findings is described by the addition of letters: maculopathy (M), tractional retinal detachment (D), neovascular glaucoma (G), and ischemic optic neuropathy (N). Systemic metabolic control of diabetes is the best means of treatment for benign retinopathy, but malignant retinopathy should immediately be seen by ophthalmologists for specific treatment: focal photocoagulation for B1, focal or panretinal photocoagulation for B2 and panretinal photocoagulation for B3-B5. Vitrectomy is indicated in B4 or more severe stages.

Diabetic Retinopathy↗

Retinopathy of prematurity: two distinct mechanisms that underlie zone 1 and zone 2 disease.

PURPOSE: In its most severe form, retinopathy of prematurity (ROP) is located in posterior retina and affects the smallest, most premature infants. We hypothesize that, depending on whether vasculogenesis (de novo formation of new vessels by transformation of vascular precursor cells (VPCs)) or angiogenesis (budding from existing vessels) is perturbed, it results in significant differences in clinical presentation and therapeutic outcome observed in zone 1 vs zone 2 ROP. DESIGN: The study is a retrospective analysis of the difference in outcome between zones 1 and 2 ROP after cryotherapy and laser therapy. METHODS: A review of the clinical presentation of zones 1 and 2 ROP that correlate this with the topography of formation of human retinal vasculature through vasculogenesis and angiogenesis. RESULTS: Population data on susceptible infants, and outcome statistics of clinical trials are given. Digital images show a correlation between ROP in zone 1 with the region of the retina vascularized through vasculogenesis. CONCLUSION: Zone 1 ROP is correlated with vessel development by vasculogenesis, relative insensitivity to laser/cryotherapy and poorer anatomic and visual outcomes. This suggests that, if the vasculogenic process is perturbed, it results in a distinct clinical presentation, poorer response to therapy, and poorer visual outcome. When the current international classification was developed, knowledge of the processes of human retinal vascular development was incomplete. The work presented here provides a framework for the development of a modification to incorporate these ideas without sacrifice of the essential elements of the international classification of ROP.

Cryotherapy↗

Ischemic retinopathy and uveitis in a patient with tetralogy of Fallot.

PURPOSE: To describe ischemic retinopathy in a patient with tetralogy of Fallot. DESIGN: Interventional case report. TESTING: Clinical and imaging evaluation. MAIN OUTCOME MEASURES: Clinical, imaging, and laboratory findings in a patient with tetralogy of Fallot. RESULTS: A 20-year-old female patient with tetralogy of Fallot had progressive visual loss of 3 weeks duration. Bilateral examination revealed dilated, tortuous, conjunctival vessels; prominent anterior chamber reaction; iris neovascularization; posterior synechia; retinal vascular tortuosity in both eyes; and inferior exudative retinal detachment. Fluorescein angiography revealed delayed retinal and choroidal filling. The working diagnosis was ischemic retinopathy with uveitis. The patient was treated for 6 months with a high-dose oral corticosteroid combined with a topical corticosteroid, a topical mydriatic, and panretinal photocoagulation. Conjunctival, vascular congestion subsided with a decrease in anterior chamber reaction. The inferior, exudative retinal detachment resolved, and vision was restored. CONCLUSIONS: Retinal ischemic syndrome combined with uveitis can develop in patients with tetralogy of Fallot. Treatment can restore vision in such patients.

Administration, Oral↗

Comparison of ultrahigh- and standard-resolution optical coherence tomography for imaging macular pathology.

OBJECTIVE: To compare ultrahigh-resolution optical coherence tomography (UHR OCT) with standard-resolution OCT for imaging macular diseases, develop baselines for interpreting OCT images, and identify situations where UHR OCT can provide additional information on disease morphology. DESIGN: Cross-sectional study. PARTICIPANTS: One thousand two eyes of 555 patients with different macular diseases including macular hole, macular edema, central serous chorioretinopathy, age-related macular degeneration (AMD), choroidal neovascularization, epiretinal membrane, retinal pigment epithelium (RPE) detachment, and retinitis pigmentosa. METHODS: A UHR ophthalmic OCT system that achieves 3-microm axial image resolution was developed for imaging in the ophthalmology clinic. Comparative studies were performed with both UHR OCT and standard 10-microm-resolution OCT. Standard scanning protocols of 6 radial 6-mm scans through the fovea were obtained with both systems. Ultrahigh-resolution OCT and standard-resolution OCT images were correlated with standard ophthalmic examination techniques (dilated ophthalmoscopy, fluorescein angiography, indocyanine green angiograms) to assess morphological information contained in the images. MAIN OUTCOME MEASURES: Ultrahigh-resolution and standard-resolution OCT images of macular pathologies. RESULTS: Correlations of UHR OCT images, standard-resolution images, fundus examination, and/or fluorescein angiography were demonstrated in full-thickness macular hole, central serous chorioretinopathy, macular edema, AMD, RPE detachment, epiretinal membrane, vitreal macular traction, and retinitis pigmentosa. Ultrahigh-resolution OCT and standard-resolution OCT exhibited comparable performance in differentiating thicker retinal layers, such as the retinal nerve fiber, inner and outer plexiform, and inner and outer nuclear. Ultrahigh-resolution OCT had improved performance differentiating finer structures or structures with lower contrast, such as the ganglion cell layer and external limiting membrane. Ultrahigh-resolution OCT confirmed the interpretation of features, such as the boundary between the photoreceptor inner and outer segments, which is also visible in standard-resolution OCT. The improved resolution of UHR OCT is especially advantageous in assessing photoreceptor morphology. CONCLUSIONS: Ultrahigh-resolution OCT enhances the visualization of intraretinal architectural morphology relative to standard-resolution OCT. Ultrahigh-resolution OCT images can provide a baseline for defining the interpretation of standard-resolution images, thus enhancing the clinical utility of standard OCT imaging. In addition, UHR OCT can provide additional information on macular disease morphology that promises to improve understanding of disease progression and management.

Adult↗

Ocular and central nervous system paracoccidioidomycosis in a pregnant woman with acquired immunodeficiency syndrome.

PURPOSE: To describe an atypical case of central nervous system and ocular paracoccidioidomycoses simulating ocular toxoplasmosis in a pregnant woman with acquired immunodeficiency syndrome (AIDS). DESIGN: Interventional case report. METHODS: Case report. RESULTS: A 25-year-old pregnant woman with AIDS, presented with a severe ocular inflammation in the right eye involving the choroid, retina, and the optic disk, which rapidly progressed to retinal detachment, iris neovascularization, and neovascular glaucoma. The left eye was normal. Magnetic resonance imaging (MRI) showed a focal hypodense contrast-enhanced ring lesion in the brain. Serum antibody titers were negative for Toxoplasma gondii, but the polymerase chain reaction was positive for the parasite in the vitreous sample. The patient responded partially to specific treatment for toxoplasmosis, and there was a small reduction in size of the brain lesion. She progressed to a blind painful eye, which was enucleated. Paracoccidioides brasiliensis was found in the histopathological studies of the eye and oropharynx. With the diagnosis of disseminated ocular paracoccidioidomycoses, the patient was treated with trimethoprim-sulfamethoxazole with a satisfactory outcome and reduction in size of the brain lesion. CONCLUSION: Although ocular infection with ocular paracoccidioidomycoses is rare, this diagnosis should be considered when investigating ocular inflammation in a patient with AIDS.

Acquired Immunodeficiency Syndrome↗

Orbital socket pain after injury.

Total retinal detachment and neovascular glaucoma occurred after a penetrating injury to the left globe that left the eye blind and painful. A retrobulbar injection of alcohol and enucleation modified but did not relieve the orbital discomfort. At surgery, we discovered a neuroma with cartilaginous metaplasia involving the supratrochlear nerve. Excision of this mass produced relief of symptoms. This is, to our knowledge, the first reported case of a neuroma with cartilaginous metaplasia involving the supratrochlear nerve.

Adult↗

Changing indications and techniques for vitrectomy in management of complications of diabetic retinopathy.

During the past two decades, the number of diabetic patients requiring vitrectomy for nonresolving vitreous hemorrhage has decreased four-fold, whereas there has been a substantial increase in diabetic patients with traction and combined traction/rhegmatogenous retinal detachment (RD) requiring surgery. Additional contemporary surgical indications are progressive fulminant neovascular proliferation, massive preretinal hemorrhage, massive fibrin response, and progressive retrolental fibrovascular proliferation. Surgical techniques for management of tractional detachments have evolved from circumscription of tractional epicenters to en bloc removal of all proliferative tissue.

Diabetic Retinopathy↗

Vitrectomy for diabetic macular heterotopia.

PURPOSE: The authors performed 15 vitrectomies for diabetic macular heterotopia, and then compared visual prognoses and postoperative complications with those of 88 macular detachments to determine the role of, and indications for, vitrectomy for diabetic macular heterotopia. METHODS: Fifteen patients with diabetic macular heterotopia and 88 with traction macular detachment, in which the vitreous cavities were sufficiently clear for posterior poles to be observed, underwent vitrectomies. Preoperative and postoperative visual acuity and postoperative complications were assessed and documented retrospectively. RESULTS: There was no statistically significant difference between the two groups in terms of eyes showing improvement in visual acuity postoperatively. However, a final postoperative visual acuity better than 20/20 was documented in 93% of patients with macular heterotopia and 48% of patients with macular detachment (P < 0.002), whereas 47% of the former and 10% of the latter had visual acuities better than 20/40 (P < 0.001). Postoperative neovascular glaucoma and retinal detachment developed in 10% and 13%, respectively, of patients with macular detachments. None of the patients with macular heterotopia experienced these complications. CONCLUSION: Based on the above results, the authors conclude that diabetic macular heterotopia is a very good indication for early vitrectomy.

Adult↗

Subretinal fibrosis in central serous chorioretinopathy.

PURPOSE: To report unusual and heretofore unreported visually damaging manifestations of severe central serous chorioretinopathy. METHODS: Case studies. RESULTS: Each of six male patients (average age, 40 years) had a form of severe central serous chorioretinopathy with at least one eye containing fibrin in the subretinal space that then developed into a subretinal fibrotic scar. Scar formation was followed by a tenting up of the macula, vascularization of the fibrosis (subretinal neovascularization), or a retinal pigment epithelial rip. Four of the seven eyes with subretinal fibrosis had severe visual loss (20/400 or worse). CONCLUSION: Subretinal fibrin and other extracellular matrix molecules appear to stimulate the retinal pigment epithelium to undergo fibrous metaplasia, which results in subretinal fibrotic scar formation and other sequelae, all of which can lead to severe visual loss.

Adult↗

Incidence of vitreoretinal pathologic conditions within 24 months after laser in situ keratomileusis.

OBJECTIVE: To report for the first time a case series of vitreoretinal pathologic conditions after laser in situ keratomileusis (LASIK) and to determine its incidence. DESIGN: Case series. PARTICIPANTS: Five refractive surgeons and 29,916 eyes that underwent surgical correction of ametropia (83.2% were myopic) ranging from -0.75 to -29.00 diopters (D; mean: -6.19 D) and from +1.00 to +6.00 D (mean: +3.23 D) participated in this retrospective study. MAIN OUTCOME MEASURES: Vitreoretinal complications after LASIK. RESULTS: The clinical findings of 20 eyes (17 patients) with LASIK-related vitreoretinal pathologic conditions are presented. Fourteen eyes experienced rhegmatogenous retinal detachments (RDs). Two eyes experienced corneoscleral perforations with the surgical microkeratome when a corneal flap was being performed (one experienced a vitreous hemorrhage and the other later experienced an RD). In four eyes, retinal tears without RDs were found. In one eye, a juxtafoveal choroidal neovascular membrane (CNVM) developed. Retinal tears were treated with argon laser retinopexy or cryotherapy. Corneoscleral perforations were sutured, and the RD was managed with vitrectomy. The remaining RDs were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The CNVM was surgically removed. The incidence of vitreoretinal pathologic conditions determined in our study was 0.06%. CONCLUSIONS: Serious complications after LASIK are infrequent. Vitreoretinal pathologic conditions, if managed promptly, will still result in good vision. It is very important to inform patients that LASIK only corrects the refractive aspect of myopia. Complications of the myopic eye will persist.

Adolescent↗

Basic fibroblast growth factor in patients with intermittent claudication: results of a phase I trial.

OBJECTIVES: This phase I study was designed to evaluate the safety, tolerability and pharmacokinetics of intra-arterial basic fibroblast growth factor (bFGF) in patients with atherosclerotic peripheral arterial disease (PVD) and intermittent claudication. We also assessed the effects of basic fibroblast growth factor (bFGF) on calf blood flow as a measure of biologic activity. BACKGROUND: Preclinical studies have shown that bFGF, an angiogenic peptide, promotes collateral development in animal models of myocardial and hind limb ischemia. The safety and efficacy of bFGF in patients is unknown, and early clinical trials are underway in coronary and peripheral arterial disease. METHODS: A double-blind, placebo-controlled, dose-escalation trial was conducted in patients with claudication demonstrating ankle/brachial index <0.8. Patients were randomly assigned to placebo (n = 6), 10 microg/kg of bFGF (n = 4), 30 microg/kg of bFGF once (n = 5) and 30 microg/kg of bFGF on two consecutive days (n = 4). Study drug was infused into the femoral artery of the ischemic leg. Detailed safety information including retinal photography for neovascularization were obtained through one year. Calf blood flow was measured with strain gauge plethysmography in the two higher dose treatment groups and in four placebo patients at baseline, one month and three to seven months after treatment. RESULTS: Intra-arterial bFGF was safe and well-tolerated. The half-life was 46 +/- 21 min. Calf blood flow increased at one month by 66 +/- 26% (mean +/- SEM) and at six months by 153 +/- 51% in bFGF-treated patients (n = 9, p = 0.002). Flow did not change significantly in the placebo group. CONCLUSIONS: In this initial randomized, double-blind, placebo-controlled trial in patients with atherosclerotic PVD and claudication, bFGF was well-tolerated. The data suggest a salutary biologic effect, and initiation of phase 2 trials is warranted.

Aged↗

In vivo transduction of photoreceptors or ciliary body by intravitreal injection of pseudotyped adenoviral vectors.

Strategies for retargeting adenoviral (Ad) vectors have been developed, but their in vivo efficacy remains to be demonstrated. Gene delivery to specific ocular cell types represents an approach to treating many diseases that cause irreversible blindness. One of these cell types, the photoreceptor (PR), is not infected by standard Ad5-based vectors. We evaluated gene delivery after intraocular injection of Ads pseudotyped with three different fiber proteins and found three distinct patterns of infection. An intravitreally injected Ad5 vector readily infected the iris, corneal endothelium, and ciliary body, while few cells in the retina expressed transgene product. In contrast, an Ad3-pseudotyped virus selectively transduced ciliary body, of interest for treating diseases such as glaucoma. A vector pseudotyped with the fiber protein of Ad37 transduced PRs as well as ciliary body. This finding has potential application to the treatment of retinal degenerative or neovascular diseases. These studies demonstrate cell type-selective gene delivery in vivo with retargeted Ads, provide information about the cellular tropisms of several Ad serotypes, and should lead to improved strategies for preserving vision.

Adenoviridae↗

[Diabetic retinopathy--pathophysiological knowledge and modern treatment methods].

Diabetic retinopathy (DR) leads to visual impairment in the majority of patients suffering from diabetes mellitus for more than 20 years. Endothelial damage, capillary dropout, and vasoproliferative activity of various growth factors are some of the complex pathophysiologic events that lead to retinal damage. Insufficient blood glucose control and arterial hypertension are the leading risk factors for the progression of DR. Adequate therapeutic measures depend on timely and regular ophthalmologic examination. Laser photocoagulation prevents severe visual loss in about 50% of cases with proliferative DR and high risk factors as defined by the Diabetic Retinopathy Study Group. Dosage of laser treatment depends on the stage and severity of DR and requires appropriate experience of the surgeon. Introduction of modern vitreoretinal surgery has yielded considerable progress in the management of vitreous hemorrhages (VH) and tractional retinal detachment in advanced stages of proliferative DR. Results of vitrectomy in 765 cases with proliferative DR are presented. Visual loss can be prevented in over 70% of cases with simple VH without retinal detachment and limited neovascularization, but in only about 30% of cases of VH complicated with retinal traction detachment and extensive vasoproliferation.

Blood Glucose↗

Disruption of the choroidoretinal interface by toxoplasma.

Toxoplasmosis is a common zoonotic infection of the retina caused by Toxoplasma gondii. The disease causes severe damage that affects the retina and subjacent choroid. Invasion of the retinal cells by the parasite leads to the major damage seen in the retina. Subsequent reactions to the invasion by toxoplasma leads to the influx of inflammatory cells. Although hypersensitivity reactions have been described to both toxoplasma and to retinal autoantigens, the major disruption of the choroidoretinal interface is probably secondary to the tissue invasion by the parasite. Patients with AIDS may show extensive necrosis of the retina in the absence of inflammatory cells. Healing of the active lesion leads to scar formation. Toxoplasma retinochoroiditis may be pigmented, nonpigmented or punched-out. Vascular anastomoses between the retina and choroid, retinal and subretinal neovascularization may occur in the aftermath of choroidoretinal interface disruption.

Animals↗