Is there any relationship between photodynamic therapy for exudative age-related macular degeneration and choroidal neovascolarization recurrence? A rationale for combined treatments.

PURPOSE: Photodynamic therapy (PDT) is the treatment of choice for subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). Interpretation of PDT mechanism of action is not yet fully understood and causes of CNV recurrences are unclear. The authors have conducted a retrospective analysis of fluorescein and indocyanine green angiographies in patients treated with multiple PDT in order to identify risk factors for recurrence. METHODS: A total of 342 eyes of 342 patients (207 women and 135 men) with ARMD and subfoveal CNV were treated with at least two PDT. Angiographic (fluorescein and indocyanine green) features of recurrences were confronted to pretreatment examinations in all patients. RESULTS: Post-PDT angiographies showed in all eyes a dark circle corresponding to the laser spot even 1 year after treatment. Persistence or progressive regrowth of CNV developed in an area adjacent or corresponding to the original lesion, without any specific relationship with the location of fluorescein and indocyanine green late leakage or with presence of abnormal fluorescence due to pigment abnormalities. At the 3-month angiographic follow-up, 23 patients (6.7%) showed a recurrent CNV resembling shape and dimension of the laser spot used for the PDT treatment. CONCLUSIONS: The authors failed to identify angiographic signs helpful to predict the risk of CNV persistence or recurrence. PDT leaves minor but persistent changes in the choroidal vasculature within the treatment area. In some cases, the recurrent CNV seems to be related to the laser spot of the PDT.

Macular function impairment in eyes with early age-related macular degeneration.

PURPOSE: To study different aspects of macular function in eyes with early age-related macular degeneration (early AMD: drusen with or without retinal pigment epithelium alterations) and normal visual acuity, to obtain a complete evaluation of macular function impairment in early AMD and to study the relationship between macular function and the ophthalmoscopic signs of early AMD. METHODS: Forty-seven subjects with early AMD and visual acuity better than 20/25 in at least one eye were studied: 34 patients had bilateral early AMD (group 1), 13 had neovascular AMD in the fellow (nonstudy) eye (group 2). Thirty-six age-matched healthy subjects were used as controls. Thirty degree stereoscopic fundus photographs and fluorescein angiography were performed to grade macular lesions. Macular recovery function, central visual field sensitivity, spatiotemporal contrast sensitivity, and the Farnsworth-Munsell 100 hue test were used to study different aspects of macular function. RESULTS: Except for color vision, all macular function tests were significantly impaired in eyes of patients with early AMD compared to those in control subjects. No functional difference was found between groups 1 and 2. The increase in drusen number negatively influenced macular recovery function. Increasing drusen confluence reduced macular recovery function as well as central visual field sensitivity and some selected spatial frequencies of spatiotemporal contrast sensitivity. Geographic atrophy of the retinal pigment epithelium and focal hyperpigmentation reduced macular recovery function and contrast sensitivity at the highest spatial frequency. CONCLUSIONS: Macular recovery function central visual field sensitivity, and spatiotemporal contrast sensitivity are adequate and reliable indicators of macular function impairment in early AMD. Macular recovery function is the test that best reflects the ophthalmoscopic characteristics of early AMD because its deterioration parallels the worsening of typical fundus lesions. Function tests are valuable in the evaluation of patients with early AMD, particularly when interventional trials are planned.

The effect of external eye irradiation on choroidal circulation.

BACKGROUND: The effect of external beam radiation therapy (teletherapy) on the choroidal circulation is poorly known. Eyes irradiated with teletherapy represent a good model to study, without confounding factors, the pathophysiologic and clinical aspects of radiation-induced chorioretinal damage. This study used fluorescein and indocyanine green choroidal angiography to investigate the late effects of external eye irradiation on the choroidal circulation. METHODS: Fluorescein angiography and indocyanine green choroidal videoangiography were performed on patients with radiation retinopathy because of external eye irradiation for orbital and paranasal sinus malignancies. Patients were divided into two groups according to the treatment field (anterior unilateral or bilateral). RESULTS: Indocyanine green angiograms showed areas of choriocapillaris hypoperfusion in all eyes-unilateral or bilateral irradiation-affected by radiation retinopathy. Late indocyanine green choroidal staining was found in five eyes (28%) of the patients who received unilateral anterior irradiation. In the same group, nine eyes (52%) had signs of choroidal precapillary occlusion and four eyes (23%) had rubeosis iridis without retinal neovascularization. One case of subfoveal choroidal neovascularization was documented in the bilateral irradiation group. CONCLUSIONS: Radiation side effects are not limited to the retinal vessels but also involve choroidal circulation. The damage to the choroid is primarily vascular, and its clinical aspects depend on the treatment fields. Anterior irradiation may be a critical factor for the appearance of unusual rubeosis iridis and neovascular glaucoma.

Macular drusen and the sensitivity of the central visual field.

Macular drusen are one of the earliest signs of age-related macular degeneration but little information is available on the functional aspects of macular area in patients with drusen. To determine if drusen are associated with changes in central visual field sensitivity, one eye of each of 35 subjects (mean age 64.9 years) with bilateral drusen and visual acuity of 1.0 (20/20) underwent automated static threshold perimetry of the central 10 degrees. 16 normal subjects (mean age 65.8 years) were used as controls. 30 degrees fundus photographs were graded in a masked fashion for the clinical characteristics of drusen: type, size and number. The mean sensitivity (MS) of the central 10 degrees was significantly lower in eyes with drusen compared to normal eyes (p = .0001). After grading drusen eyes for size (> or = 63 mu) and type (presence of soft drusen), MS significantly deteriorated when large and soft drusen were present. These results suggest that central visual field sensitivity is precociously affected in eyes with drusen and that testing central visual field sensitivity may be useful as functional parameter in long term studies on the evolution of age-related macular degeneration.

Age-related macular degeneration.

Age-related macular degeneration (AMD), a bilateral, progressive macular disease, represents the major cause of blindness among elderly people living in Western countries. Clinical features of AMD vary from the initial asymptomatic aspects, drusen and retinal pigment epithelium alterations, to severe atrophic or exudative changes in the advanced stages, characterized by the irreversible decrease of visual function. Current epidemiologic, pathogenetic and clinical data are reviewed, and the importance of the exact identification of patients at risk of evolution toward the exudative form is addressed. The therapeutic approach to AMD is also analyzed and the role of laser photocoagulation is discussed.

The effect on the macular function of laser photocoagulation for diabetic macular edema.

The benefit of focal and grid-laser photocoagulation in reducing the risk of visual loss from diabetic macular edema has been established. In order to investigate the effect of this treatment on macular function, 30 diabetics with macular edema and 1.0 visual acuity were tested before and after laser treatment at intervals of 1 week, and 1 and 3 months, respectively. The test was carried out by means of nyctometry, contrast sensitivity, hue discrimination and critical flicker frequency of blue cones. All patients had abnormal results in macular tests before treatment. During the follow-up, visual acuity remained stable and the macular tests did not statistically modify, except for nyctometry, which deteriorated at the 1-week follow-up (P = 0.02) and then increased to the basal values, and contrast sensitivity [improved at the last control (P = 0.006)]. Clinical regression of macular edema was observed, but macular function tests never normalized. Patients with diabetic macular edema and good visual acuity should be monitored with many functional methods, and laser treatment should be performed before macular function deteriorates irreversibly.

Effects of ionizing radiation on human conjunctival epithelial cells: a clinical and cytologic study.

In order to identify early and late modifications induced by ionizing radiation on the conjunctival surface, we studied 10 patients irradiated for paranasal sinus tumors. A clinical and morphological study of conjunctival epithelium (using an impression cytology technique) was performed; 5 patients were examined during and the others after treatment. Actinic conjunctivitis and keratitis, observed during treatment, reappeared within a few months after the end of radiotherapy. At a threshold dose of 25 Gy, chronic nuclear changes and cellular surface disorganization of the conjunctival epithelium were found--these progressed and persisted. Our data support the importance of careful monitoring of such irradiated patients and the benefit of planning a prospective clinical study to evaluate the effects of available drugs (all-trans retinoic acid) in the treatment of these lesions.

The epidemiology and prevalence of diabetic retinopathy in the Veneto region of north east Italy. Veneto Group for Diabetic Retinopathy.

The prevalence of diabetic retinopathy and its relationship to a number of risk factors were examined in a population-based study in the Veneto region of North East Italy. Of 1321 diabetic patients selected, 98% attended for examination. Prevalence of diabetic retinopathy was 26.2% (24.4% background and 1.8% proliferative). The prevalence of retinopathy was significantly related (p less than 0.01) to the duration of diabetes (17.3% for less than 5 years; 60.8% for greater than 20 years). Proliferative retinopathy was much more prevalent after 20 years of diabetes. After 10 years most proliferative retinopathy was found in Type 1 diabetic patients, but before 10 years from diagnosis it was most prevalent in Type 2 diabetes. The prevalence of retinopathy was significantly related (p less than 0.001) to the type of diabetes and was found predominantly in Type 1 (46.2%) and insulin-treated Type 2 (45.9%) subjects and to a lesser degree in non-insulin-treated patients (24.6%). The prevalence of retinopathy was significantly related to both fasting and post-prandial blood glucose levels (p less than 0.001), blood urea nitrogen (p less than 0.05), and systolic (p less than 0.001) and diastolic (p less than 0.01) blood pressure. No significant differences were found in the prevalence of total or proliferative retinopathy between males and females. No significant relationships were found with family history of diabetes, alcohol intake, smoking habits, cholesterol, triglycerides, and serum uric acid.

Branch retinal vein occlusion: the pathogenetic role of blood viscosity.

The pathogenesis of branch retinal vein occlusion has not been completely clarified. The role of abnormal blood viscosity in the appearance and evolution of the disease has recently been advocated. We studied 54 patients with long-standing branch retinal vein occlusion from a hemorrheologic point of view. Depending on the extension of retinal ischemia, two subgroups were identified. Hematocrit, blood and plasma viscosity, whole blood filterability, cell deformability, and fibrinogen levels were investigated. Thirty-five subjects of similar age, sex, and risk factors of diabetes and hypertension served as controls. Our results showed that blood viscosity is higher in patients with occlusion and particularly in those with severe retinal ischemia. Statistical analysis showed a direct correlation between blood viscosity and hematocrit.

Macular recovery function (nyctometry) in diabetics without and with early retinopathy.

Nyctometry was used to assess macular recovery function in 234 diabetic patients; their retinopathy ranged from no retinopathy (99) to early background retinopathy (135). None had visual symptoms or macular oedema. Abnormal (reduced) nyctometry findings were significantly and directly related to the deterioration of diabetic retinopathy. There was no significant association between reduced or normal nyctometry findings and glycaemia at the time of the examination. The value of nyctometry in screening and follow-up is discussed.

The role of fluorescein angiography in the interpretation of optic nerve head diseases.

In normal individuals fluorescein angiography of the optic nerve head has some peculiar signs. Three early phases can be distinguished, they include: 1) retrolaminar and laminar filling, 2) prelaminar filling, 3) superficial capillary filling. A late staining is also part of the fluorescein angiography of a normal disc. Many optic nerve disturbances show changes of the above mentioned angiographic signs. The Authors discuss the fluorescein angiographic pattern of 1) anterior ischemic optic neuropathy, 2) central retinal vein occlusion, 3) papilledema and 4) drusen.

[Sorsby's pseudo-inflammatory macular dystrophy: laser treatment]. / Dystrophie maculaire pseudo-inflammatoire de Sorsby: essai de traitement par le laser.

In 1949, Sorsby described a familial fundus disease with progressive visual loss and bilateral hemorrhages and exudates of the posterior pole. The dystrophy, whose inheritance was apparently autosomal dominant, was called pseudo-inflammatory macular dystrophy because of extensive macular lesions that could suggest a post-inflammatory change. The ophthalmoscopic signs include the presence of diffuse drusen-like deposits with extensive changes of retinal pigment epithelium and focal atrophy of the choriocapillaris, particularly in the posterior pole. Some eyes grow subretinal neovascularization, which appears associated to retinal edema, deep hemorrhages and hard exudates. These cases ultimately result in a disciform macular scar. Atrophy of peripheral fundus is typical of advanced stages. We present the case of three sisters whose fundus lesions resembled Sorsby's pseudo-inflammatory macular dystrophy. In two of them, where there was a great suspicion of macular subretinal neovascularization, the laser treatment seemed to positively condition the course of the disease. In our opinion, even though a generalized atrophy of the choroid and retina cannot probably be avoidable, laser treatment can delay the loss of central vision, by blocking the capillaries from leaking, thus preventing secondary destruction from bleeding and fibrosis.

Fluorescein angiography of the optic nerve head in the elderly.

Interpretation of fluorescein angiography of the optic nerve head is somewhat difficult due to its peculiar vasculature. Three early phases can commonly be observed: 1) retrolaminar and prelaminar filling; 2) prelaminar filling; 3) superficial capillary filling. The authors describe the characteristics of the fluorescein angiography of norman optic nerve hed in the elderly. The interpretation of these signs is also discussed.

Studies on the retina of the diabetic db/db mouse. I. Endothelial cell-pericyte ratio.

The genetically diabetic db/db mouse is a model of type-2 diabetes, where nephropathy and neuropathy, but not retinopathy were observed. The authors studied the retinas (trypsin digestion technique) of 16 db/db mice and 16 age-matched litter mates (db/m; controls), divided into five age groups. They noted a marked increase in the ratio of endothelial cells to intramural pericytes in diabetic mice compared to controls. This increase resulted from a selective and highly significant loss of pericytes in db/db mice (p less than 0.05). Some strand-like and relatively acellular capillaries were also observed. The db/db mouse may represent an adequate model for studies on the pathogenesis of retinopathy.

Prevalence of microangiopathic complications in hyperglycemia secondary to pancreatic disease.

Diabetes secondary to pancreatic disease (PD) represents a useful model for the study of the effects of chronic hyperglycemia on microangiopathic complications in the absence of those genetic factors predisposing to Type I diabetes. Our aim was to evaluate the prevalence of nephropathy and retinopathy in a group of 86 patients with PD. The genetic pattern, assessed by the determination of HLA antigens, was different than in patients with Type I diabetes. A family history of diabetes was present in 53% of the patients. The prevalence of retinopathy was 37%. Eighteen percent of the patients with duration of diabetes less than 10 years showed an albumin excretion rate (AER) greater than 40 mg/24 hr. The prevalence of pathologic microalbuminuria (greater than 40 mg/24 hr) was found in 29% of the patients with duration of diabetes greater than 10 years. The prevalence of pathologic microalbuminuria is related to the duration of diabetes. Both diastolic and systolic blood pressure is positively correlated to albumin excretion rate (p less than 0.02), suggesting a possible role of hypertension in the evolution of nephropathy. Sixty-one percent of the patients with AER greater than 40 mg/24 h had retinopathy, thus confirming the close association between renal and ocular complications. Abnormal microalbuminuria and retinopathy were not influenced by a family history of diabetes. We conclude that the prevalence of microangiopathic complications is similar to that seen in Type I diabetes, and the metabolic abnormalities of diabetes can play a direct role in the development of diabetic microangiopathy.

Retinopathy following radiation therapy of paranasal sinus and nasopharyngeal carcinoma.

Radiation retinopathy is a complication of the therapeutic irradiation of orbital and periorbital structures. The authors studied two groups of patients who had orbital (group 1) and periorbital (group 2) external irradiation. Radiation retinopathy occurred in 63.6% of patients in group 1 and 36.3% group 2. Retinal radiation damage showed a different clinical evaluation in the two groups, appearing earlier (mean, 11 versus 55 months) and with greater involvement of the peripheral retina in group 1 (with three cases of neovascular glaucoma). This study demonstrates that radiation retinopathy occurs in a significant number of cases when the eye is not totally involved in the irradiation field and shows at least two different clinical aspects in relation to the radiation treatment. It also suggests that portal design and choroidal circulation damage may represent important factors in the development of radiation retinopathy.

Optic nerve involvement in diabetic retinopathy.

The Authors briefly review the problem of the involvement of optic nerve head in patients affected by diabetic retinopathy. It is suggested that optic nerve damage is always the result of a microvascular disorder involving the optic disc area. Diabetic papillopathy is considered in detail.