Treatment of macular degeneration (a controlled case)

Our controlled case describes the drug possibility to stabilize the exudative form of Age-related Macular Degeneration. The new approach of selective destruction of choroidal neovascularization (CNV) can be applied in patients with subfoveal lesions. Photodynamic therapy (PDT) is based on the reaction of photoactivable drug with the light of low-energy laser beam. So far only verteporfin [Visudyne, Novartis] as sensitizer is marketed and laser with wavelength of 689 nm is used. But it is questionable whether to apply this very costly treatment to extremely old people. An example of treatment of 90-year old woman with AMD with classic form of CNV is presented. Her BCVA was 0.05 OD. She underwent four session of PDT. At the last visit (eighteen months after initial and ten months after last session of PDT) the BCVA remained 0.05 OD. The patient is using a special magnifying lens for reading achieving near vision of 0.32. The presented example indicates the necessity of detailed study of every case to promote the therapeutic decisions for the benefit of progress in the field.     

Ultraviolet sun radiation and incidence of age-related macular degeneration on Croatian Island Rab

This epidemiological study is completed on island Rab, located in North Adriatic Sea. For this study it is important that Adriatic Sea has one of the highest solar radiations in geographical area of Europe. The aim of this epidemiological study is to estimate correlation between incidence of Age-Related Macular Degeneration (AMD) and exposure of sunlight in two different populations on island Rab. In the first group of population of island Rab, agriculturists and fishermen (n = 1300), incidence of AMD was in 18%, but in urban population only 2.5%. It is very interesting that correlation exists between incidence of AMD and exfoliation syndrome. In the group of chronic exposure to sunlight (agriculturists and fishermen) exfoliation syndrome exists in 28%, but in urban population it has never been seen. The age in both populations was 45-65 years. We can conclude that there is a very significant correlation between chronic exposure to sunlight and appearance of AMD.     

Age-related macular degeneration is not macular process only--peripheral retina is attacked too

On a small island of Rab, geographical latitude 44 degrees 40' N, with the highest solar radiation among Adriatic islands, 1371 patients were examined in 2003-2005 period, with the aim of estimating the frequency of the patients number with Age-related Macular Degeneration (AMD), and further if the peripheral retina is damaged similarly as the macular region. In the first group of agriculturists and fishermen (n = 1300) we estimated the AMD, initial and middle stage of AMD, in 18% of population, but in urban population only by 2 patients. Perimetric analysis with computerized Kowa perimeter, estimated that the peripheral retina is affected similarly as the macular region. Author concludes that for this reason, the usual term of "Age-related Macular Degeneration" should necessarily be named with the suffix "Peripheral", or "Age-related Retinopathy".     

Evaluation of oxidative stress, 3-Nitrotyrosine,and HMGB-1 levels in patients with wet type Age-Related Macular Degeneration

BackgroundThis study aims to compare serum HMGB-1, 3-nitrotyrosine (3-NT), TAS, TOS, and OSI levels in Wettype Age-Related Macular Degeneration (wAMD) patients and healthy controls to determine the correlation of these parameters with each other.MethodsThirty patients with Wet-type Age-Related Macular Degeneration (wAMD) and 27 healthy adults, as controls were enrolled in the study. We determined the TAS and TOS levels in serum samples of both groups using commercial kits on a microplate reader. Serum HMGB-1 and 3-NT levels were measured with the enzyme-linked immunosorbent assay method.ResultsHMGB-1 levels were significantly higher in the patient group (137.51 pg/mL, p=0.001), while there was no difference between the two groups in serum 3-NT levels (p=0.428). A statistically significant difference found in the levels of TOS and OSI (p=0.001 and p=0.045, respectively) between the patients and controls, however, no significant difference was observed between the groups in terms of TAS levels (p=0.228).ConclusionsOxidative stress and HMGB-1 levels were increased in wAMD patients and enhanced oxidative stress may be associated with increased tissue necrosis and inflammation. Thus administration of antioxidant treatment in addition to routine therapy should be considered in wAMD.     

Epidemiological study of sun exposure and visual field damage in children in Primorsko-Goranska County--the risk factors of earlier development of macular degeneration

The aim of this study was to examine the possible harmful effects of solar exposure on visual field damage in children living in Primorsko-Goranska County. Our previous work has shown noxious influence on visual field in children with anamnesis long term exposure to sunlight. This is an extended study, including children in Novi Vinodolski and Gorski kotar. We measured possible defect in isopteric visual field and macular-meridian thresholds. In the area of island of Rab these changes were the biggest, subsequently is Novi Vinodolski and at least Gorski kotar with the smallest range of eye complicates according to exposure to sunlight. These damages correlate with the areas of great solar emission. Damages in periphery isopters of visual field have shown the characteristics of periphery defect invagination, while increased macular thresholds in complete visual field was from 5 to 15Asb. We can conclude that there is direct connection between increased sunlight and long-term exposure to sunlight on one side, and on the other side, damages of retinal perception. Increased sun exposure may represent very important factors in early occurrence and develop of Age-Related Macular Degeneration (AMD). It is recommended the children protection in summer months, as well as taking derivates of vitamin A and antioxidants. Nowadays, AMD is one of the most important causes of damaged visual field, pretend to be national problem if we don't use the adequate prevention. World Health Organization has to begin with prevention of AMD, including these risk factors.     

Prednisolone neuroprotective therapy in age-related macular degeneration

134 patients with Age-related Macular Degeneration (AMD) (aging 47-75 years) were treated in therapy procedure with parabulbar injections of Methylprednisolone Acetate and Prednisolone Acetate. In the first group of patients with AMD (n = 71 patients) were treated with Methylprednisolone acetate, and second group (n = 63 patients) with Prednisolone acetate. Each patient was given doses of 60 mg, through two weeks, 10 mg every second day. It's estimated in all patients ameliorate in macular threshold, so that it's in the group with Methylprednisolone treatment, ameliorate effect begins after first week, than in second group, treated with Prednisolone, initial ameliorate effect is after second week. Complete effect in both groups is after 2 months. It can be concluded that the treatment of AMD with glucocorticoids has the ameliorate effect in vision loss and it is decided that earlier effect in the group treated with Methylprednisolone, is probably of higher affinity for glucocorticoid receptors.     

Designing and testing scene enhancement algorithms for patients with retina degenerative disorders

Background  

Retina degenerative disorders represent the primary cause of blindness in UK and in the developed world. In particular, Age Related Macular Degeneration (AMD) and Retina Pigmentosa (RP) diseases are of interest to this study. We have therefore created new image processing algorithms for enhancing the visual scenes for them.     

Self referral to an accident and emergency department for another opinion.

OBJECTIVE--To determine whether patients referring themselves to an accident and emergency department for another opinion after consulting their general practitioner present with serious illness, show any risk factors for being admitted, or are more likely to be patients of particular practitioners. DESIGN--Six month prospective survey. SETTING--District general hospital''s accident and emergency department, receiving 42,000 new patients a year. PATIENTS--180 Patients identified as attending for another opinion having already consulted a general practitioner. INTERVENTIONS--Classified as admission, referral to specialist clinic, follow up in accident and emergency department, or referral back to general practitioner. END POINT--Admission, with an analysis of admitted patients. MEASUREMENTS AND MAIN RESULTS--General outcome, diagnostic category, age, time of attendance, time since seen by general practitioner, and name of general practitioner were recorded. Forty seven patients were admitted, 99 were discharged back to the general practitioner (62 without a letter), and two died. Patients were most likely to be admitted if they attended within 24 hours after seeing a general practitioner, were aged under 5, or presented with respiratory or gastrointestinal complaints. Some general practitioners were overrepresented. CONCLUSIONS--Important disorders present in this way, and therefore these patients should be seen by a doctor. Information about these attendances could be useful to general practitioners in reviewing their performance.     

Lipids,oxidized lipids,oxidation-specific epitopes,and Age-related Macular Degeneration

Age-related Macular Degeneration (AMD) is the leading cause of blindness among the elderly in western societies. While antioxidant micronutrient treatment is available for intermediate non-neovascular disease, and effective anti-vascular endothelial growth factor treatment is available for neovascular disease, treatment for early AMD is lacking due to an incomplete understanding of the early molecular events. The role of lipids, which accumulate in the macula, and their oxidation, has emerged as an important factor in disease development. These oxidized lipids can either directly contribute to tissue injury or react with amine on proteins to form oxidation-specific epitopes, which can induce an innate immune response. If inadequately neutralized, the inflammatory response from these epitopes can incite tissue injury during disease development. This review explores how the accumulation of lipids, their oxidation, and the ensuing inflammatory response might contribute to the pathogenesis of AMD. This article is part of a Special Issue entitled: Lipid modification and lipid peroxidation products in innate immunity and inflammation edited by Christoph J. Binder .     

Isolation and characterization of a spontaneously immortalized bovine retinal pigmented epithelial cell line

Background  

The Retinal Pigmented Epithelium (RPE) is juxtaposed with the photoreceptor outer segments of the eye. The proximity of the photoreceptor cells is a prerequisite for their survival, as they depend on the RPE to remove the outer segments and are also influenced by RPE cell paracrine factors. RPE cell death can cause a progressive loss of photoreceptor function, which can diminish vision and, over time, blindness ensues. Degeneration of the retina has been shown to induce a variety of retinopathies, such as Stargardt's disease, Cone-Rod Dystrophy (CRD), Retinitis Pigmentosa (RP), Fundus Flavimaculatus (FFM), Best's disease and Age-related Macular Degeneration (AMD). We have cultured primary bovine RPE cells to gain a further understanding of the mechanisms of RPE cell death. One of the cultures, named tRPE, surpassed senescence and was further characterized to determine its viability as a model for retinal diseases.     

Understanding hospital referral rates: a user's guide.

Detailed referral information from one practice was used to investigate the effect of calculating referral rates in several different ways. Referral rates for individual general practitioners should be related to the number of consultations carried out and not to the number of registered patients; for whole practices list size may be used as the denominator. Most doctors will not need to control for age and sex of patients when comparing referral rates but may need to control for case mix when comparing referral rates to individual specialties. In addition, a method is described for distinguishing systematic variation between the referral rates of individual doctors from the random variation that may arise from data based on fairly small numbers of referrals. The method indicates whether systematic variation is greater than would be expected by chance, and it can be extended to indicate whether variability in referral rates is greater in one specialty than another. Because of random variation with time a year''s data may not be sufficient to allow reliable interpretation of referral rates to individual specialties, except for the largest. At present there is no known relation between high or low referral rates and quality of care. Nevertheless, if doctors are to interpret their own rates of referral they need those rates to be reliable and valid. Use of the 10 guidelines described in this paper will help to prevent unwarranted conclusions being drawn from information on general practitioners'' rates of referral to hospital.     

What associates Charles Bonnet syndrome with age-related macular degeneration?

Charles Bonnet syndrome (CBS) is a condition related to patients with visual loss due to age related macular degeneration or glaucoma that are having complex visual hallucinations. The CBS was first described by Swiss physician Charles Bonnet in 1760. Affected patients, who are otherwise mentally healthy people with significant visual loss, have vivid, complex recurrent visual hallucinations (VHs). One characteristic of these hallucinations is that they usually are "Lilliputian hallucinations" as patients experience micropsia (hallucinations in which the characters or objects are distorted and much smaller than normal). The prevalence of Charles Bonnet Syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. The high incidence of non-reported CBS is thought to be as a result of patient's fear to report the symptoms as they could be labeled as mentally insane since those type of visual hallucinations could be found in variety of psychiatric and neurological disorders such as drug or alcohol abuse (delirium tremens), Alice in Wonderland syndrome (AIWS), psychosis, schizophrenia, dementia, narcolepsy, epilepsy, Parkinson disease, brain tumors, migraine, as well as, in long term sleep deprivation. VHs can also be presented as the initial sign of the Epstein-Barr virus infection in infectious mononucleosis. Patients who suffer from CBS usually possess insight into the unreality of their visual experiences, which are commonly pleasant but may sometimes cause distress. The hallucinations consist of well-defined, organized, and clear images over which the subject has little control. It is believed that they represent release phenomena due to deafferentiation of the visual association areas of the cerebral cortex, leading to a form of phantom vision. Cognitive defects, social isolation, and sensory deprivation have also been implicated in the etiology of this condition. This study was conducted on 350 patients diagnosed with Age-Related Macular Degeneration (AMD) and shows incidence of CBS in 13% of patients with AMD. Furthermore, we have found higher incidence of CBS in patients with massive loss of vision in peripheral visual field which is not age related.     

Detection of Early Age-Related Macular Degeneration Using Novel Functional Parameters of the Focal Cone Electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration.     

Do clinical guidelines improve general practice management and referral of infertile couples?

OBJECTIVE--To evaluate guidelines for general practice management and referral of infertile couples. Guidelines were implemented with a disease specific reminder at the time of consultation (the guidelines were embedded within a structured infertility management sheet for each couple). DESIGN--Pragmatic randomised controlled trial. Participating practices were randomised to a group that received the guidelines and a control group. SETTING--82 general practices in Grampian region. SUBJECTS--100 couples referred by general practitioners receiving the guideline and 100 couples referred by control general practitioners. MAIN OUTCOME MEASURES--Whether the general practitioner had taken a full sexual history and examined and investigated both partners appropriately. RESULTS--Characteristics of patients referred by study and control general practitioners did not differ significantly at baseline. Compliance with the guidelines increased for all targeted activities. General practitioners in the study group were more likely to take a sexual history (for example, couples'' use of fertile period, 85% v 69%, p < 0.01); examine both partners (female partner, 68% v 52%, p < 0.05; male partner 39% v 13%, p < 0.01); and investigate both partners (day 21 progesterone, 72% v 41%, p < 0.001; semen analysis, 51% v 41%, p > 0.05). Improvements were greater when general practitioners used the disease specific reminder. CONCLUSION--Receiving guidelines led to improvements in the process of care of infertile couples within general practice. This effect was enhanced when the guidelines were embedded in a structured infertility management sheet for each couple.     

Influence of Royal College of Radiologists' guidelines on referral from general practice. Royal College of Radiologists Working Party.

OBJECTIVE--To measure the effect on general practitioner referrals for radiography of introducing guidelines of good practice together with monitoring and peer review. DESIGN--Collection of referral data during 1 January 1989 to 31 December 1990. Guidelines were introduced on 1 January 1990. SETTING--Open access radiology services provided by one non-teaching district in England. SUBJECTS--144614 registered patients from 22 practices. MAIN OUTCOME MEASURES--Number of referrals per 1000 registered patients for radiography of the chest, skull, spine, abdomen, limbs, and joints and for barium investigation and excretion urography. RESULTS--Overall referrals fell from 88.4/1000 registered patients to 77.2/1000 after the guidelines were introduced. The commonest reasons for referral were for examination of the chest, spine, and limbs and joints and referrals for these fell by 9.4%, 17.5%, and 13.5% respectively. Referrals for skull radiography fell by 30% (from 241 to 168). CONCLUSIONS--By helping general practitioners to be more selective in their use of diagnostic radiology, the guidelines reduced the rate of referral and thus patients'' exposure to radiation.     

Raised intraocular pressure: an alternative method of referral.

To assess delay in referring patients with suspected glaucoma two methods were studied in a randomised trial: direct referral from optician to ophthalmologist and referral through the patient''s general practitioner. Direct referral was reliable for all 49 patients involved, whereas, of the 44 patients referred through their general practitioner, seven waited over three weeks for referral.     

General practitioners' referrals to specialist outpatient clinics. I. Why general practitioners refer patients to specialist outpatient clinics.

There has been much concern about the wide variations in general practitioners'' referral rates and the consequent implications for cost and quality of care. This has led to a call to evaluate the appropriateness and effectiveness of referrals. A collaborative audit of referrals to outpatient clinics was conducted by 127 general practitioners in 33 practices in the Oxford region. Records were kept of 18,754 referrals, which included data on diagnoses and reasons for referral. Overall, 6553 (35.4%) of the referrals were for particular treatments or operations and a further 6475 (34.9%) were for specific investigation or diagnosis. Advice on management was the main reason for referral in 2656 (14.3%) cases, and in 1719 (9.3%) cases the general practitioners wanted the consultants to take over managing their patients. Reassurance of either the general practitioner or the patient was recorded as the main reason in only 762 (4.1%) referrals. There seems to be scope for rationalising the referral process. A programme with three stages for evaluating referrals to outpatient clinics is recommended.     

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18 :213–9). A woman with a high‐grade cytological lesion, a repeated low‐grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow‐up for each woman seen. Reflex testing for high‐risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow‐up of low‐grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high‐grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC‐H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow‐up of special cases such as women who are pregnant, postmenopausal or immunocompromised.     

Dramaturgical study of meetings between general practitioners and representatives of pharmaceutical companies

ObjectivesTo examine the interaction between general practitioners and pharmaceutical company representatives.DesignQualitative study of 13 consecutive meetings between general practitioner and pharmaceutical representatives. A dramaturgical model was used to inform analysis of the transcribed verbal interactions.SettingPractice in south west England.Participants13 pharmaceutical company representatives and one general practitioner.ResultsThe encounters were acted out in six scenes. Scene 1 was initiated by the pharmaceutical representative, who acknowledged the relative status of the two players. Scene 2 provided the opportunity for the representative to check the general practitioner''s knowledge about the product. Scene 3 was used to propose clinical and cost benefits associated with the product. During scene 4, the general practitioner took centre stage and challenged aspects of this information. Scene 5 involved a recovery strategy as the representative fought to regain equilibrium. In the final scene, the representative tried to ensure future contacts.ConclusionEncounters between general practitioners and pharmaceutical representatives follow a consistent format that is implicitly understood by each player. It is naive to suppose that pharmaceutical representatives are passive resources for drug information. General practitioners might benefit from someone who can provide unbiased information about prescribing in a manner that is supportive and sympathetic to the demands of practice.

What is already known on this topic

Pharmaceutical representatives influence physicians'' prescribing in ways that are often unacknowledged by the physicians themselvesMeetings with pharmaceutical representatives are associated with increased prescribing costs and less rational prescribing

What this study adds

Meetings between pharmaceutical representatives and general practitioners follow a consistent format that is implicitly understood by each playerGeneral practitioners may cooperate because representatives make them feel valued     

Avoidable referrals? Analysis of 170 consecutive referrals to secondary care.

OBJECTIVE--To determine appropriateness of referrals from primary care to secondary care. DESIGN--Retrospective evaluation of appropriateness of referrals from a single-handed general practice: evaluations carried out independently by referring doctor and by second general practitioner who worked in same area and had access to similar secondary care services. SUBJECTS--168 referrals made between 1 October 1990 and 31 March 1991 and followed up for up to 12 months by matching with available information on outcome of episode of care. MAIN OUTCOME MEASURES--Appropriateness of referral and reasons for inappropriate referrals. RESULTS--110 referrals were agreed to be appropriate and 58 were considered avoidable. The reason for 32 of the inappropriate referrals was lack of resources: 10 were due to lack of information (mainly failure of hospitals to pass on information to general practitioner), nine were due to a deficient primary health care team; five were due to insufficient use of home care nurses, three were due to absence of direct access to day hospital, and five were due to lack of access to general practitioner beds or other facilities. Most of the remaining 26 avoidable referrals were because available resources had not been fully used, because recognised management plans had not been followed, or because of lack of skills to perform certain procedures. CONCLUSIONS--Many theoretically avoidable referrals were due to managers'' and politicians'' decisions about allocation of resources, but some inappropriate referrals could be avoided by assessment of general practitioners'' needs for further knowledge and skills.