[IMMUNITY PROCESSES IN THE PATHOGENESIS OF INFLAMMATORY DISEASES (AND THEIR RELATION TO EYE DISEASES)].
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Antibody Formation↗
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Diabetes and thyroid-related eye disease.
Diabetes and thyroid-related eye disease cause significant morbidity. Although these are endocrine disorders, they cause different ocular manifestations. Previously unexamined epidemiologic factors offer new insight to diabetic eye disease. The association of hyperglycemia, systemic medical therapy, and visual loss is reviewed. Although retinopathy remains the leading cause of blindness, multiple "nonretinal" diabetic ocular problems occur and how these correspond with retinopathy is examined. Thyroid-related eye disease, as seen in Graves' ophthalmopathy, is an autoimmune process. This is reexamined and new ultrasound techniques to measure disease activity are described. The advantage of therapies directed against these features is reported.
Animals↗
[Comparative study of the role of cytokines in different forms of eye diseases. 1. Tumor necrosis factor-alpha].
Local and total-systems production of tumor necrosis factor-alpha (TNF) is studied in 214 patients with different clinical forms of inflammatory and other than inflammatory diseases of the eyes. Healthy donors were controls. A total of 265 blood sera, 335 lacrimal fluid samples, and 9 specimens of subretinal fluid were examined. The pathogenetic role of TNF was most persuasively confirmed for corneoscleral injuries, proliferative diabetic retinopathy, and total detachment of the retina. Local and systemic cytokine hyperproduction observed in these patients was associated with a grave course and unfavorable outcomes. One more manifestation of immunopathology was pronounced imbalance between the cytokine content in the lacrimal fluid and serum, which was observed in patients with active bilateral uveitis, extensive detachments of the retina, and complicated cataracts. The unfavorable impact of TNF deficiency during the development of a pathological process in the eye (early stages of diabetic retinopathy, burns, and contusions of the eye) is discussed. Clinical and immunological data validate the efficacy of TNF test for predicting the course of an eye disease, monitoring its treatment, and assessing the desirability of immunocorrection.
Contusions↗
Thyroid eye disease--medical or surgical therapy?
Thyroid eye disease is autoimmune in nature and associated with Graves' Disease. Autoantibodies to the 64 kDa antigen in thyroid membranes cross-react to the 64 kDa proteins in human eye muscle membranes. Antibody dependent cell mediated cytotoxicity against eye muscle cells are also found in patients with thyroid eye disease. The purpose of this paper is to review the treatment available and to share the authors' experience using cyclosporin A. In the majority of cases, thyroid eye disease is mild, manifest only as bilateral or unilateral proptosis, with/without grittiness of the eyes. This is usually treated conservatively with eye drops. If proptosis is more severe and there is incomplete closure of eyelids, epiphora and conjunctival injection, then lateral tarrsorrhaphy is usually effective, combined with use of eye pads and eye drops. The problem of diplopia can be treated conservatively with special lenses, or with surgical correction of tethered muscles. However when proptosis is severe, with raised intraocular pressure, severe chemosis and danger of blindness, then the choice of therapy is controversial: rapid decompression by surgical means or use of high doses of prednisolone. Most prefer prednisolone therapy initially, surgical decompression if it fails. Various other methods have been tried, aimed at the immunological nature of the disease, namely plasmapheresis, radiotherapy and immunosuppressive drugs such as cyclosporin, with variable success. Our experience with cyclosporin had been mixed and inconclusive.
Cyclosporins↗
A contribution to the knowledge about autoimmune eye diseases.
In this paper the autoimmune eye disease complex is presented in detail. The problems of autoagressivity in the light of new conceptions based on modern microchemical, chemical and immunological methods of analysis that allow better insight in the nature of these diseases are discussed. The basic concepts of immunological mechanisms and autoimmunity are explained, with special attention given to those occurring in the eye. Attention is directed towards the importance of various intra- and extraocular factors, as well as to the regulatory mechanisms that influence the autoimmune eye disease's development. In the conclusion the authors analyze the abilities and aims of further investigations of this field of ophthalmoimmunopathology.
Autoimmune Diseases↗
The STIR sequence MRI in the assessment of extraocular muscles in thyroid eye disease.
Nineteen patients with thyroid eye disease were examined with magnetic resonance imaging using the Short Tau Inversion Recovery (STIR) sequence and compared with normal controls. The Signal Intensity Ratio (SIR) of each of the four recti was obtained by comparison with the signal intensity of the adjacent temporalis muscle. The SIR was compared with disease activity assessed using Werner's grading system, a clinical inflammatory score, and the range of extraocular movements. Results show that a high SIR is associated with a high index of disease activity. This technique is likely to prove useful in assessing disease activity and planning the management of thyroid eye disease, particularly with respect to immunosuppression.
Adult↗
Advances in the diagnosis and management of AIDS-related eye disease.
AIDS-related eye disease is changing rapidly. New clinical entities have been reported, most numerous of which are the uveitis syndromes in patients with elevated CD4+ counts. Advances in management of cytomegalovirus retinitis (CMVR) include laser demarcation as an alternative to vitrectomy with silicone oil injection in macula-sparing cytomegalovirus-related retinal detachments and discontinuation of maintenance therapy in select patients with quiescent CMVR and elevated CD4+ counts. Screening guidelines have been proposed for childhood CMVR. Serial fundus photography has been recommended to improve follow-up evaluation of CMVR. A method to improve intraocular lens calculation in silicone-filled eyes has been offered. The rapidity and extent to which drug resistant cytomegalovirus infection develops has been elucidated. And the controversy of oral ganciclovir prophylaxis for cytomegalovirus disease has been argued from several angles. The following article reviews these and other advances in the understanding of AIDS-related eye disease.
AIDS-Related Opportunistic Infections↗
Endoscopic orbital decompression for dysthyroid eye disease.
Orbital decompression for dysthyroid eye disease is traditionally performed either through an external approach or transantrally. The introduction of endoscopic sinus surgery over the last decade has led to a better understanding of the intranasal surgical landmarks of orbital walls and the development of endoscopic orbital decompression. We have adopted the endoscopic technique as the treatment of choice for orbital decompression in dysthyroid eye disease for the last two years. The surgical technique is described and illustrated, and the results of our first series of 15 patients (30 orbits) are presented.
Adult↗
Trends in cost of major eye diseases to Medicare, 1991 to 2000.
PURPOSE: To estimate impacts of physician-diagnosed eye diseases (age-related macular degeneration (AMD), cataract, diabetic retinopathy, and glaucoma) on Medicare payments in the periods 1991 to 1995 and 1996 to 2000. DESIGN: A retrospective cohort study to estimate program payments per capita and in total for each of the major eye diseases and the four eye diseases in total. METHODS: Data from the 1994 and 1999 National Long-Term Care Survey (NLTCS) and medical claims to Medicare from 1991 to 2000 were merged with the NLTCS. Medicare payments for eye-related procedures on persons with and without major eye diseases as reported on Medicare claims and self-reported data from NLTCS. RESULTS: Overall, the burden of major eye diseases was to increase Medicare spending by 4.8 billion dollars (1999 USD) in 1991 to 1995 and by 4.5 billion dollars in 1996 to 2000. The most expensive eye disease was cataract, costing Medicare 3.8 billion dollars in 1991 to 1995 and 3 billion dollars in 1996 to 2000. CONCLUSIONS: Prevalence of major eye diseases increased over time, but the effect of major eye diseases on Medicare payments decreased, mainly as a result of lower payments for cataract surgery in the later years.
Aged↗
Awareness of eye diseases in an urban population in southern India.
OBJECTIVE: To assess the level of awareness of eye diseases in the urban population of Hyderabad in southern India. METHODS: A total of 2522 subjects of all ages, who were representative of the Hyderabad population, participated in the population-based Andhra Pradesh Eye Disease Study. Of these subjects, 1859 aged > 15 years responded to a structured questionnaire on cataract, glaucoma, night blindness and diabetic retinopathy to trained field investigators. Having heard of the eye disease in question was defined as "awareness" and having some understanding of the eye disease was defined as "knowledge". FINDINGS: Awareness of cataract (69.8%) and night blindness (60.0%) was moderate but that of diabetic retinopathy (27.0%) was low, while that of glaucoma (2.3%) was very poor. Knowledge of all the eye diseases assessed was poor. Subjects aged > or = 30 years were significantly more aware of all eye diseases assessed except night blindness. Multivariate analysis revealed that women were significantly less aware of night blindness (odds ratio (OR) = 0.78; 95% confidence interval (CI) = 0.63-0.97). Education played a significant role in awareness of these eye diseases. Study subjects of upper socioeconomic status were significantly more aware of night blindness (OR = 2.20; 95% CI = 1.29-3.74) and those belonging to upper and middle socioeconomic strata were significantly more aware of diabetic retinopathy (OR = 2.79; 95% CI = 2.19-3.56). Muslims were significantly more aware of cataract (OR = 2.36; 95% CI = 1.84-3.02) and less aware of night blindness (OR = 0.52; 95% CI = 0.42-0.64). The major source of awareness of the eye diseases was a family member/friend/relative suffering from that eye disease. CONCLUSION: These data suggest that there is a need for health education in this Indian population to increase their level of awareness and knowledge of common eye diseases. Such awareness and knowledge could lead to better understanding and acceptance of the importance of routine eye examinations for the early detection and treatment of eye diseases, thereby reducing visual impairment in this population.
Adolescent↗
The spectrum of eye disease in children with AIDS due to vertically transmitted HIV disease: clinical findings, virology and recommendations for surveillance.
BACKGROUND: Eye disease in children infected with HIV is uncommon, but there is little information on which children require screening or surveillance and the management of those with retinitis. METHODS: We examined 12 children with symptomatic HIV disease (of a cohort of 98 HIV-positive children) using indirect ophthalmoscopy. When retinitis was found it was documented photographically at the time of diagnosis and on follow-up. RESULTS: Four cases of infective retinitis were diagnosed: three with probable cytomegalovirus retinitis and one with progressive outer retinal necrosis. CONCLUSION: Detection of reactivation is difficult and we recommend fundus photography under general anaesthesia wherever possible. Children with other end-organ disease, symptomatic eye disease and advanced HIV disease with severe immunosuppression require ophthalmological surveillance.
Acquired Immunodeficiency Syndrome↗
[Treatment of chronic eye diseases in Bad Hall].
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Balneology↗
Thyroid eye disease (TED)--a current understanding.
Thyroid Eye Disease (TED) provides a clinical meeting place for physician, ophthalmologist and immunologist. Some past difficulties in understanding this disease may have reflected too narrow specialization. In this presentation only three eponymous terms will be used --Graves' Disease, Plummer's Disease and Hashimoto's Disease.
Eye Diseases↗
Thyroid Eye Disease.
The treatment of thyroid eye disease is very complex, owing to the varied nature of the symptoms and the variable course of the disease. The first step in treatment should be achieving an euthyroid state or monitoring for the development of hyperthyroidism if the patient is euthyroid at presentation. The second step is local measures (artificial tears and ointment, cessation of smoking) along with careful visual follow-up (acuity, color vision, automated visual fields, fundus examination, ocular motility, and external examination) to assess for the development of optic neuropathy, proptosis, diplopia, and lid abnormalities. If external irritation or orbital discomfort cannot be managed with conservative local measures, then a trial of oral corticosteroids or orbital radiation can be considered. If optic neuropathy develops without proptosis, corticosteroids--starting with an intravenous course, then oral medication--should be used. If there is either an initial improvement in optic neuropathy with corticosteroids, but worsening with subsequent tapering of corticosteroids or no initial improvement, radiation treatment or orbital decompression can be done. If optic neuropathy develops with proptosis, corticosteroids--starting with an intravenous course, then oral medication--should be used for rapid visual improvement. Orbital decompression should then be done to resolve both the optic neuropathy and the proptosis. If for medical reasons the patient with optic neuropathy and proptosis is not a surgical candidate, then radiation treatment can be done, but there will be little change in the proptosis. Proptosis without optic neuropathy can be treated with orbital decompression both for cosmetic reasons and for comfort. Occasionally, this will also resolve lid retraction, and return the lids to an acceptable position in terms of cosmesis and corneal exposure. Diplopia is best treated initially with press-on prisms or patching. Once the disease is stable (ie, no variation in proptosis or change in ocular motility measurements for at least 6 months), eye muscle surgery can be planned. Eye muscle surgery should follow orbital decompression because there is a reasonable possibility that decompression will change ocular motility. If there is corneal exposure or unacceptable lid position and proptosis is not an issue, eyelid surgery, at times on both upper and lower lids, can be done. Eyelid surgery should follow eye muscle surgery because a change in eye position, particularly with vertical muscle surgery, can change eyelid position. Finally, the patient should be made aware at the time of diagnosis that there is unlikely to be a return to normal appearance (ie, appearance before the development of thyroid eye disease).
Journal Article↗
Prevention of herpes simplex virus eye disease: a cost-effectiveness analysis.
OBJECTIVES: To estimate the cost of treating herpes simplex virus (HSV) eye disease, and to evaluate the incremental cost-effectiveness of chronic suppressive antiviral prophylaxis for reducing ocular HSV recurrences. METHODS: An economic decision-tree model was used on follow-up data from 703 patients with prior ocular HSV disease who were enrolled in a Herpetic Eye Disease Study multicenter clinical trial that evaluated the prolonged use of oral acyclovir. Costs were based on wholesale drug prices, Medicare fees, and national health surveys. Incremental cost-effectiveness ratios for all patients and for patients with prior stromal keratitis were calculated as the additional net cost of acyclovir prophylaxis compared with the number of cases of ocular herpes prevented during 12 months. One- and 2-way sensitivity analyses evaluated the effect of different treatment costs and recurrence risks. RESULTS: Approximately 17.7 US dollars million is expended annually to treat the estimated 59,000 new and recurrent episodes of HSV eye disease occurring among 29,000 individuals each year in the United States. Chronic suppressive oral acyclovir costs 8532 US dollars per ocular HSV episode averted. The incremental cost per infection averted would decline by up to 51% if antiviral prophylaxis were more effective and by up to 87% if patients had a higher recurrence risk. Targeting prophylaxis to patients with a history of stromal keratitis is not more cost-effective than providing oral acyclovir for patients with any prior HSV eye disease. CONCLUSIONS: Herpetic eye disease is costly to treat and prevent. Because prophylactic oral acyclovir is not a cost-effective option for all patients with previous HSV eye disease, therapeutic decisions must be made on a case-by-case basis.
Acyclovir↗
Prevalence of diabetic eye disease in an inner city population: the Liverpool Diabetic Eye Study.
PURPOSE: To measure the population prevalence of diabetic eye disease in an inner city setting. METHODS: As part of a systematic screening programme all adult diabetic patients in four general practices were invited to attend for slit-lamp biomicroscopy by a retinal specialist. Data on non-attenders were available from community-based photography. RESULTS: Of 395 diabetic patients identified, 326 attended biomicroscopy with photographic data available on a further 31, giving a 90% compliance rate. Point prevalence of diabetes in the target population was 12.4/ 1000. Demographic data included: mean age 60 years (range 13-92 years); type of control: type I 49, type II insulin-requiring (IR) 40, type II non-insulin-requiring (NIR) 268. Prevalences were as follows: any retinopathy: of all diabetic patients 33.6%, type I 36.7%, type II IR 45.0%, type II NIR 31.3%; proliferative/ advanced: all 1.1%, type I 2.0%, type II IR 0, type II NIR 1.1%; clinically significant macular oedema: all 6.4%, type I 2.3%, type II IR 16.2%, type II NIR 5.7%. The percentage of patients with retinopathy requiring follow-up by an opthalmologist was 4.5%, and 9.2% had macular exudates within 1 disc diameter of fixation or significant circinate maculopathy. Sight-threatening diabetic eye disease (STED) was found in 13.4%. A visual acuity of < or = 6/24 in the better eye occurred in 12 (3.4%) patients and of < or = 6/60 in the better eye in 3 (0.8%). CONCLUSIONS: Compared with previous population studies, prevalences appear to have declined in type I, but remain high in type II diabetic patients and especially in those requiring insulin.
Adolescent↗
Protection against herpes simplex virus-induced eye disease after vaccination with seven individually expressed herpes simplex virus 1 glycoproteins.
PURPOSE: To compare the efficacy of each of seven expressed herpes simplex virus 1 (HSV-1) glycoproteins as vaccines to protect against ocular disease after primary ocular HSV-1 infection. METHODS: Mice were vaccinated three times with equal amounts of each of seven individually expressed HSV-1 glycoproteins (gB, gC, gD, gE, gG, gH, and gI) and then ocularly challenged with McKrae, a corneal disease-producing strain of HSV-1. Viral clearance from the eye, blepharitis, keratitis, and neovascularization were determined at various times after infection. RESULTS: Mice vaccinated with gD or gB had the best protection against eye disease. Vaccination with gI, gC, or gE produced moderate protection against eye disease. Vaccination with gG produced less protection, and vaccination with gH produced no apparent protection against eye disease. CONCLUSIONS: These results suggest that when used as vaccines, different HSV-1 glycoproteins provide different levels of protection against HSV-1-induced eye disease. Based on comparison with the authors' previously published results, the ability of each glycoprotein to protect against eye disease correlated with the ability of the glycoprotein to induce high serum neutralizing antibody titers and killer cell activity. Results suggest that the effectiveness of these seven glycoproteins in protecting against eye disease can be ranked as follows: gD > gB > gI > (gC = gE) > gG > gH.
Animals↗
Retention time for corticosteroid-sparing systemic immunosuppressive agents in patients with inflammatory eye disease.
BACKGROUND: Multiple immunosuppressive drugs have been used to manage inflammatory eye disease when control cannot be achieved by corticosteroid alone. However, although clinical studies support the effectiveness of most of these agents, comparative studies have not been undertaken. Retention time, a measure of the duration of treatment with any given drug, is a crude indicator of drug effectiveness and tolerability that facilitates such a comparison. The retention time was compared for corticosteroid-sparing immunosuppressive agents in patients attending our tertiary referral inflammatory eye disease clinic. METHODS: The clinical records of all patients attending an inflammatory eye disease clinic at the Casey Eye Institute over a 1-year period (2003) were reviewed. From these records, we collected the following clinical data: age; sex; ocular diagnosis; and use of steroid-sparing systemic immunosuppression, including drugs, duration of treatment and, if ceased, reasons for cessation. Cox regression analysis, adjusted for clustering, was used to compare other drugs against methotrexate. RESULTS: 107 of 302 (35%) patients seen at the inflammatory eye disease clinic in 2003 had a total of 193 current or past prescriptions for systemic steroid-sparing immunosuppressive agents. The treated group, most of whom had uveitis, included 32 men and 75 women, aged 5-86 years. Most commonly prescribed were methotrexate (66 uses, 34%), ciclosporin (37 uses, 19%), azathioprine (26 uses, 13%), mycophenolate mofetil (22 uses, 11%) and cyclophosphamide (15 uses, 8%). Patients were retained significantly less on ciclosporin (p = 0.004), azathioprine (p = 0.04), mycophenolate mofetil (p = 0.04) and cyclophosphamide (p<0.001) compared with methotrexate. Reasons for cessation included adverse events, lack of effectiveness, success or remission, cost and desire for fertility. CONCLUSIONS: In patients with inflammatory eye disease, methotrexate may offer a superior combination of effectiveness and tolerability over other commonly used corticosteroid-sparing immunosuppressive agents. In this study, there was a twofold risk of not being retained on azathioprine, mycophenolate mofetil and ciclosporin and a fourfold risk of not being retained on cyclophosphamide compared with methotrexate.
Adolescent↗