Choroidal neovascularization not associated with age-related macular degeneration

Choroidal neovascularization (CNV) is an important clinical finding that is associated with many ocular conditions, including inflammatory, infectious, degenerative, hereditary, and congenital disorders, ocular tumors, trauma, and a few miscellaneous disorders. The growth of new choroidal vessels beneath the retinal pigment epithelium is associated with specific clinical signs. The clinical recognition of CNV plays a key role in the prognosis and management of these disorders. The clinical presentation of each disorder associated with CNV is reviewed in this paper, with comments on the location and the frequency of CNV occurrence.     

Slow photostress recovery and disease severity in age-related macular degeneration

SETTING: The Matiben Chest Clinic at the West Algiers University Teaching Hospital, and 3 outpatient clinics specializing in tuberculosis and lung disease in Algiers. OBJECTIVE: To determine the tolerance and efficacy of a fixed proportion combination of 3 antituberculosis drugs (per tablet: 50 mg isoniazid + 120 mg rifampicin + 300 mg pyrazinamide) given during the first 2 months of a daily 6-month chemotherapy regimen. DESIGN: Random prospective treatment trial comparing a group of 124 patients receiving the triple combination with another group of 126 patients receiving the 3 drugs separately during the initial treatment phase. The continuation phase was identical for the 2 groups. Comparison of tolerance in the first 2 months, and of the failure and relapse rates (respectively at the end of treatment and 24 months after the end of treatment). RESULTS: During the first 2 months side-effects were significantly more common in the group receiving the drugs separately. At the end of treatment and during the following 24 months there were no significant differences in the cumulative rates of observed failures and relapses (2% and 1%). CONCLUSION: The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven.     

Photoreceptor loss in age-related macular degeneration

PURPOSE: The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the fundus. If so, AMD must have a predilection for rods over cones. The authors tested this hypothesis by determining the relative numbers of cones and rods in donor eyes with mid-to late-stage AMD and in age-matched controls. METHODS: Thirteen eyes (from seven donors) with grossly visible macular drusen and pigmentary disturbances were either wholemounted for photoreceptor counts or sectioned through the fovea for histopathology and carbonic anhydrase histochemistry to label red-green cones. Eyes were assigned to AMD or control groups on the basis of histopathology and clinical history. RESULTS: Five nonexudative AMD (NE-AMD) eyes from three donors showed sparing of foveal cones and loss of rods and cones in the parafovea. In two donors, rod loss exceeded cone loss at most parafoveal locations, and in one donor, rod density was normal and cone density was reduced. In eight exudative AMD (EX-AMD) eyes from five donors, photoreceptors surviving along the margins of and overlying disciform scars were largely cones. CONCLUSIONS: Photoreceptors are lost in NE-AMD as well as in the more severe exudative form, consistent with functional and clinical studies. The authors propose that rods die in older eyes without evidence of overt retinal pigment epithelial disease. In persons susceptible to AMD, the retinal pigment epithelium becomes dysfunctional. Secondarily, rod loss continues and cones begin to degenerate. Eventually, only degenerate cones remain; ultimately, all photoreceptors may disappear.     

The genetics of age-related macular degeneration

Age-related macular degeneration (ARM) is a progressive, chronic condition that results when the macula degenerates and central vision is lost. ARM is the leading cause of vision loss in Americans over age 50 and is a major public health concern. Very little is known about the etiology of ARM. Deciphering the genetic susceptibility associated with ARM holds great promise for gaining a better understanding of the disease, identifying at-risk individuals, and developing interventions and treatments.     

Cigarette smoking and age-related macular degeneration

BACKGROUND: Age-related macular degeneration (ARMD) is one of the leading causes of severe visual impairment among older Americans. Several hypotheses have been proposed regarding the pathogenesis of ARMD. The possible association of cigarette smoking and ARMD remains controversial. METHODS: Studies concerning the relationship between cigarette smoking and ARMD are identified through the use of Vision Articles Online and PubMed. Articles published since 1970 are reviewed. RESULTS: The literature reviewed strongly supports a link between smoking and ARMD. CONCLUSIONS: The identification of smoking as a risk factor can lead to early intervention. Such intervention may lessen visual loss from this disease, which has limited medical treatment options.     

Increase in interphotoreceptor matrix gelatinase A (MMP-2) associated with age-related macular degeneration

Matrix metalloproteinases have increasingly been shown to be associated with diseases involving neovascularization and/or abnormal cellular migration or proliferation. A number of diseases of this type affect the retina. In this study, the activity of gelatinase A (MMP-2), the most abundant matrix metalloproteinase in IPM (interphoto receptor matrix) and vitreous, was measured with respect to age in normal human donor eyes and compared to donors with age-related macular degeneration. IPM and vitreous were obtained from a total of 88 human donors. Samples for electrophoresis were normalized for protein content and subjected to quantitative gelatin zymography. The zymograms were scanned and then digitized and quantitated using the NIH 'Image' program. There was not a statistically significant change in the level of gelatinase A in IPM or vitreous as a function of age, although a slight downward trend was found in the total gelatinase A activity within the normal population. Likewise, when comparing normal and age-related macular degeneration donors, there was not a significant difference in the gelatinase A level in vitreous or in retina-associated IPM. However, the level of gelatinase A was nearly doubled specifically in retinal pigment epithelium-associated IPM from eyes with age-related macular degeneration [0.99 +/- 0.09 U mg-1 (56) vs 1.71 +/- 0.28 U mg-1 (14) (mean +/- S.E.M. (number), P < 0.0021; 1 unit = 1.0 ng gelatin cleaved h-1). Gelatinase A may be associated with the changes that occur in age-related macular degeneration, especially the neovascularization which accompanies the exudative ('wet') form of the disease.     

Genetic association of apolipoprotein E with age-related macular degeneration

Several investigators have studied the deficit in maximal voluntary force that is said to occur when bilateral muscle groups contract simultaneously. A true bilateral deficit (BLD) would suggest a significant limitation of neuromuscular control; however, some of the data from studies in the literature are equivocal. Our purpose was to determine whether there is a BLD in the knee extensors of untrained young male subjects during isometric contractions and whether this deficit is associated with a decreased activation of the quadriceps, increased activation of the antagonist muscle, or an alteration in motor unit firing rates. Twenty subjects performed unilateral (UL) and bilateral (BL) isometric knee extensions at 25, 50, 75, and 100% maximal voluntary contraction. Total UL and BL force (delta 3%) and maximal rate of force generation (delta 2.5%) were not significantly different. Total UL and BL maximal vastus lateralis electromyographic activity (EMG; 2.7 +/- 0.28 vs. 2.6 +/- 0.24 mV) and coactivation (0.17 +/- 0.02 vs. 0.20 +/- 0.02 mV) were also not different. Similarly, the ratio of force to EMG during submaximal UL and BL contractions was not different. Analysis of force production by each leg in UL and BL conditions showed no differences in force, rate of force generation, EMG, motor unit firing rates, and coactivation. Finally, assessment of quadriceps activity with the twitch interpolation technique indicated no differences in the degree of voluntary muscle activation (UL: 93.6 +/- 2.51 Hz, BL: 90.1 +/- 2.43 Hz). These results provide no evidence of a significant limitation in neuromuscular control between BL and UL isometric contractions of the knee extensor muscles in young male subjects.     

Advanced glycation end products in age-related macular degeneration

OBJECTIVE: To investigate the localization of N epsilon-(carboxymethyl)lysine (CML), a component and major immunologic epitope of advanced glycation end products, in aged eyes and choroidal neovascular membranes (CNVMs) surgically excised from eyes with age-related macular degeneration. METHODS: Immunohistochemistry for CML was performed using 8 snap-frozen, surgically excised CNVMs. Twelve eyes from patients aged 69 to 82 years and 2 donor eyes, 1 each from a 23-week-old fetus and 21-year-old patient, without age-related macular degeneration or diabetic retinopathy were also examined. To determine if retinal pigment epithelial cells in CNVMs accumulate advanced glycation end products, cytokeratin and CML were stained in paired serial sections. RESULTS: Soft, macular drusen and/or basal laminar and basal linear deposits were observed in 8 of 12 aged eyes. Each case showed CML accumulation, while overlying retinal pigment epithelial cells showed no accumulation in all 12 eyes. In CNVMs, however, retinal pigment epithelial cells showed CML accumulation in their cytoplasm. CONCLUSION: The additional accumulation of advanced glycation end products in soft, macular drusen and/or retinal pigment epithelial cells may play a role in the pathogenesis of CNVM formation in age-related macular degeneration. CLINICAL RELEVANCE: Recently, advanced glycation end products have been found to play a role both in aging changes and neovascularization. Localization of advanced glycation end products in the above-mentioned tissue may lead to a better understanding of the pathogenesis of age-related macular degeneration.     

HTLV-I associated myelopathy with macular degeneration

The authors report a case of macular involvement in a patient with HTLV-I associated myelopathy (HAM). The patient was a 10-year-old girl who noticed sudden decreased vision in her right eye in November 1987. The corrected visual acuity was 0.01 in the right eye and 1.0 in the left eye. Fundus examination of the right eye disclosed mild optic disc pallor. The macula appeared to have pigmentary mottling with superficial irregular retinal reflex that was three disc diameters in size. Fluorescein angiography revealed a discoid hypofluorescent area in the macula, surrounded by mottled hyperfluorescent areas. She had no contributory family history of ocular disease, but had a history of blood transfusion during an operation for patent ductus arteriosus and ventricular septal defect at the age of 8 months. In November 1990, she developed gait disturbance due to spastic paraparesis and was admitted to our hospital. Antibodies to HTLV-I were markedly elevated in serum (titer, 1:8192) and in cerebrospinal fluid (titer, 1: 1024). She was diagnosed as HAM. Two months later, she developed encephalopathy and bilateral optic disc atrophy.     

The short-wavelength mechanisms of Stiles in age-related macular degeneration

Clinical measurements by the increment-threshold technique of W.S. Stiles are reported in five cases of age-related macular degeneration. Measurements were made on a modified Tübingen perimeter using 1 degree, short-wavelength targets presented on a red field.     

韦企平教授治疗年龄相关性黄斑变性经验介绍

年龄相关性黄斑变性又称老年性黄斑变性,为黄斑部视网膜的退行性病变,患者发病年龄多在50岁以上,是老年人致盲的主要原因之一,严重影响患者生活质量,目前西医对该病尚无有效治疗方法.中医眼科韦氏眼科第4代传人北京中医药大学韦企平教授运用中医方法治疗该病经验丰富,验案颇多.现将其经验总结介绍如下.     

Clinical experience with the Ben-Sira teledioptric system for use in age-related macular degeneration

Hanita-Ben-Sira has recently developed a bifocal optical implant with central hyperminus and peripheral positive components that is used in conjunction with specially constructed spectacles to improve visual performance in patients with age-related macular degeneration. The Ben-Sira teledioptric system was evaluated in 17 patients. It produces a magnified image of high and improved resolution and an enlargement of the visual field. It is easy to use and increases the reading distances.     

Choroidal neovascularization in second eyes of patients with unilateral exudative age-related macular degeneration

PURPOSE: To evaluate patients with unilateral occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) for the nature of the neovascularization which develops in the fellow eyes. METHODS: Patients with newly diagnosed unilateral occult CNV were followed prospectively for the development of CNV in the fellow eye. Patients were classified based on the type of occult CNV in the first eye: (1) those with associated serous pigment epithelial detachment (serous PED) and (2) those without. Demographic and clinical data, including the type of CNV in the second eyes, were compared. RESULTS: Choroidal neovascularization developed in 115 patients in the second eye. Fifty-six patients had occult CNV with a serous PED (also termed vascularized PED) in the first eye, and 59 patients had occult CNV without serous PED. The two groups did not differ significantly in the demographic and the clinical features evaluated. Well-delineated (or classic) CNV developed in the fellow eye of one patient in each group. Of the remaining 55 patients with vascularized PED in the first eye, the same type of occult CNV developed in 48 (87%) patients in the second eye. Of 58 (84%) patients in the second group, the same type of occult CNV developed in the second eye of 49 patients. This symmetric distribution of type of CNV between eyes is highly significant (P < 0.001). CONCLUSIONS: Eyes with occult CNV secondary to AMD can be classified by the presence or absence of an associated serous PED. Patients with unilateral occult CNV have a significant risk of occult CNV developing in the second eye, and the type of occult disease in the first eye is highly predictive of the type of neovascularized disease in the second eye. These findings are important with respect to natural history, and possibly to the treatment response and visual prognosis of patients with neovascularized AMD.     

Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease

Mutation scanning and direct DNA sequencing of all 50 exons of ABCR were completed for 150 families segregating recessive Stargardt disease (STGD1). ABCR variations were identified in 173 (57%) disease chromosomes, the majority of which represent missense amino acid substitutions. These ABCR variants were not found in 220 unaffected control individuals (440 chromosomes) but do cosegregate with the disease in these families with STGD1, and many occur in conserved functional domains. Missense amino acid substitutions located in the amino terminal one-third of the protein appear to be associated with earlier onset of the disease and may represent misfolding alleles. The two most common mutant alleles, G1961E and A1038V, each identified in 16 of 173 disease chromosomes, composed 18.5% of mutations identified. G1961E has been associated previously, at a statistically significant level in the heterozygous state, with age-related macular degeneration (AMD). Clinical evaluation of these 150 families with STGD1 revealed a high frequency of AMD in first- and second-degree relatives. These findings support the hypothesis that compound heterozygous ABCR mutations are responsible for STGD1 and that some heterozygous ABCR mutations may enhance susceptibility to AMD.     

Visual results after submacular surgery for neovascularization in age-related macular degeneration

Orthopedists being more engaged in surgery are often asked about problems concerning exercise science. This article will summarize the existing basic knowledge, very close to practice, and put down the leading steps of how to build up a (therapeutical) training programme. A lab block is recommended acting on a preventive as well as on a sportive medical base.     

Perifoveal laser treatment for subfoveal choroidal neovascularization in age-related macular degeneration

The management of subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration presents a major therapeutic dilemma. No treatment may lead to severe visual loss, and direct laser treatment to the entire subfoveal lesion results in acute loss of visual acuity. Encouraging results have been described with a foveal-sparing laser technique for subfoveal CNV. The authors performed perifoveal confluent laser treatment on a relatively well-defined occult CNV, sparing the foveal avascular zone. One month after treatment, the visual acuity had improved from 20/400 to 20/30. At 24 months, the visual acuity was 20/40 with no recurrence. Confluent perifoveal laser treatment for subfoveal CNV may be useful in preserving central visual acuity in selected patients.     

The course of age-related macular degeneration following bilateral cataract surgery

OBJECTIVE: The aim of this study was to define the relative regulation of matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinases-1 (TIMP-1), in chondrocytes and synovium in experimental osteoarthritis (EOA). METHODS: Partial-meniscectomized (PM) rabbits, surgical sham controls (SH), and normal non-surgical controls (N) were killed at times corresponding to early degenerative lesions (4 weeks) and increasingly progressive stages of EOA at 8 and 12 weeks post-PM. MMP-3 activity was measured in conditioned media from chondrocytes and synovium using a peptide cleavage assay with substance P (SP) as the substrate. TIMP-1 was quantitated using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Early degenerative lesions (4 weeks post-PM) were characterized by inflammatory responses in the synovium accompanied by a significant rise of MMP-3 activity in synovial cultures (P < 0.05). At 8 weeks there was no discernible inflammation, and MMP-3 activity in EOA synovial cultures was comparable to that in the controls; this was followed by a second increase in MMP-3 activity in EOA samples at 12 weeks. MMP-3 activity was significantly elevated in EOA chondrocyte cultures at 8 weeks post-PM relative to N controls, corresponding to the most destructive phase of EOA, but not in the early phase (4 weeks) or 'late' degenerative phase (12 weeks). Medium derived from chondrocytes contained little or no TIMP-1. Synovia secreted relatively higher amounts of TIMP-1, and this was elevated at 8 weeks post-PM relative to the SH controls. The majority (approximately 90%) of MMP-3 activity could be inhibited using recombinant TIMP-1 or a hydroxamate MMP inhibitor. Complete inhibition was achieved with EDTA or 1,10 phenanthroline. CONCLUSION: Together, these data indicate that in EOA, MMP-3 is initially upregulated in the synovium which may play a pivotal role in the pathogenesis of cartilage lesions. In contrast, chondrocyte-derived MMP-3 is upregulated in the later phases of EOA, contributing further to progression of cartilage lesions.