The effect of therapy refusal against medical advice in retinoblastoma patients in a setting where treatment delays are common.

BACKGROUND: Patients who refuse therapy against medical advice may be at risk of adverse health outcomes. We analyzed the impact of therapy refusal and its effect on the survival of retinoblastoma patients. PATIENTS AND METHODS: 165 consecutive untreated retinoblastoma patients admitted to the CM-Hospital, between 1993-2000 were evaluated retrospectively. Survival outcomes and its association with delays and tumor staging were analyzed using Kaplan-Meier and Cox-Regression. RESULTS: Of the 165 cases, 78 cases (47,3%) were assigned to the "No-Refusal-Group"; 52 cases (31,5%) to "Temporary-Refusal-Group," 30 cases (18,2%) to "Definite-Refusal-Group." Survival rates of patients who temporarily refused were significantly lower than those who did not refuse the therapy (p < 0.05). Progression of tumor stage was highly associated with temporary-refusal (p < 0.0005). In the Cox-Regression model, clinical staging of tumor was highly associated, whereas admission delay and treatment delay were slightly associated with the overall survival (p < 0.05, adjusted-hazard-ratio 6.321, 1.031,1.025, respectively). The clinical staging is the strongest variable associated with patient survival outcome. Delay >or= 6 months between first sign and admission is highly associated with tumor progression (p < 0.0005). CONCLUSIONS: First, the high level of therapy refusal in a developing country like Indonesia has an adverse effect on the survival outcome of retinoblastoma patients. Second, the change of the tumor stage from intraocular to extraocular is the most adverse predictive factor for survival. Third, the advanced stage of the tumor is caused by long delay to admission. In a developing country the parents of many young patients refuse to accept the recommended therapy and therefore the tumor may reach a critical stage for the prognosis.

Evaluation of cross-sectional and longitudinal construct validity of two vision-related quality of life questionnaires: the LVQOL and VCM1.

The Low Vision Quality of Life (LVQOL) questionnaire and the Vision-related Quality of Life Core Measure (VCM1) are two of the many vision-related quality of life (QOL) questionnaires that have been developed in recent years. Although psychometric properties of the LVQOL and VCM1 compare well with other vision-related QOL questionnaires, construct and longitudinal validity have not been assessed (adequately). The purpose of this study was to examine the cross-sectional and longitudinal construct validity of these questionnaires by testing specific pre-specified hypotheses about the relations of these questionnaires with other measures. The percentage of hypotheses regarding the cross-sectional construct validity that were refuted for the LVQOL was 22% for the basic aspects of vision subscale, 50% for the mobility subscale, 39% for the adjustment subscale and 17% for the reading and fine work subscale. For the VCM1 this percentage was 57%. For the longitudinal construct validity the percentage of hypotheses that were refuted ranged from 33 to 75% for the LVQOL subscales and was 50% for the VCM1. In conclusion, cross-sectional construct validity was satisfactory for the LVQOL subscales, but seemed poor for the VCM1. In addition, the longitudinal validity of these scales was poor to moderate.

Clinical evaluation of the pressure phosphene tonometer in patients with glaucoma.

AIM: To evaluate the reliability of the pressure phosphene tonometer in comparison with the Goldmann applanation tonometer. METHODS: 45 consecutive patients with glaucoma (78 eyes) participated in the study. Eyes with previous eye surgery, a documented peripheral visual field defect, a refractive error of more than 5 dioptres, and patients who were unable to understand the procedure were excluded from the study. Intraocular pressure was measured with a pressure phosphene tonometer by one examiner and with a Goldmann applanation tonometer by two other examiners no more than 15 minutes apart. A second series of measurements was performed several weeks later on 34 patients (59 eyes). There was no communication between examiners or between examiner and patient regarding test results. RESULTS: No statistically significant correlation was found between the applanation tonometry values and those obtained with a pressure phosphene tonometer. CONCLUSION: The pressure phosphene tonometer is not suitable for reliably measuring intraocular pressure.

Measurement of stray light and glare: comparison of Nyktotest, Mesotest, stray light meter, and computer implemented stray light meter.

AIM: To evaluate the properties of devices for measuring stray light and glare: the Nyktotest, Mesotest, "conventional" stray light meter and a new, computer implemented version of the stray light meter. METHODS: 112 subjects, divided in three groups: (1) young subjects without any eye disease; (2) elderly subjects without any eye disease, and (3) subjects with (early) cataract in at least one eye. All subjects underwent a battery of glare and stray light tests, measurement of visual acuity, contrast sensitivity, refraction, and LOCS III cataract classification. Subjects answered a questionnaire on perceived disability during driving. RESULTS: Repeatability values were similar for all glare/stray light tests. Validity (correlation with LOCS III and questionnaire scores), discriminative ability (ability to discriminate between the three groups), and added value (to measurement of visual acuity and contrast sensitivity) were all superior for both stray light meters. Results of successive measurements are interrelated for the conventional but not the new stray light meter. This indicates a better resistance to fraud for the latter device. CONCLUSIONS: The new computer implemented stray light meter is the most promising device for future stray light measurements.

Orofacial granulomatosis in a patient with Crohn's disease.

Orofacial granulomatosis encompasses the previously recognized clinical entities Melkersson-Rosenthal syndrome and cheilitis granulomatosa. We report the case of a 39-year-old patient with cheilitis granulomatosa, intestinal Crohn's disease, and optic neuropathy. Cheilitis granulomatosa and optic neuropathy represent 2 rare manifestations of orofacial granulomatosis in Crohn's disease.

[Diagnostic image (155). A man with facial emphysema. Subcutaneous facial emphysema due to dental cleaning]. / Diagnose in beeld (155). Een man met emfyseem van het gelaat. Subcutaan faciaal empyseem door gebitsreiniging.

A 47-year-old man developed subcutaneous emphysema of the right side of his face during a dental cleaning procedure by the dentist.

Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus.

PURPOSE: To determine the normal spectrum of ocular complications and associated visual outcome in patients with herpes zoster ophthalmicus. METHODS: This prospective observational cohort study included 73 immunocompetent adults with herpes zoster ophthalmicus, referred by their general practitioners within 7 days of skin rash onset. The follow-up period was 6 months. All patients received a 7-14-day course of systemic aciclovir treatment combined with longterm application of a lubricating ophthalmic ointment as long as the corneal epithelium was affected. Topical corticosteroids were strictly avoided in the acute phase of ocular disease. Acquired visual loss scores at 1, 2 and 6 months were based on best corrected visual acuity (BCVA) level and evaluation of the ophthalmological history and findings. RESULTS: Ophthalmic herpes zoster led to a variety of transient inflammatory reactions within the anterior eye segment of the involved side in 46 patients (63%), but did not seriously compromise their ultimate visual outcome. Mild to moderate visual loss, with corrected VA between 0.3 and 0.8, was found in 17 patients at 1 month (23%), in 10 patients at 2 months (14%) and in seven patients at 6 months follow-up (10%). None of the patients developed visual loss with a corrected VA of less than 0.3. CONCLUSION: Functional vision was retained in all ophthalmic zoster patients referred to the ophthalmologist in the acute phase of the disease by vigorous antiviral treatment and adequate prevention of corneal exposure.

Histocompatibility and corneal transplantation.

BACKGROUND: HLA typing and matching have been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations were performed by a single surgeon in a single center between 1976 and 1996. Population genetic and other statistical analyses were performed. Simulation studies assessed the effects of HLA-DR mistypings on analytical results. RESULTS: Mono- and multivariate analyses identified retransplantation, degree of vascularization, HLA-AB and -DR match grades, endothelial cell count, graft size, recipient gender, storage method and panel-reactive antibodies as significantly influencing the survival of corneal transplants. Simulation studies showed that the beneficial effect of HLA-DR matching is abrogated by HLA-DR mistypings. CONCLUSIONS: Corneal transplant recipients have a normal immune response to HLA incompatibilities. Demonstration of that fact requires accurate HLA typings.

Relation between perceived driving disability and scores of vision screening tests.

AIM: To determine the relation between perceived driving disability and vision screening tests. METHODS: 93 subjects, aged 50 years and over, with binocular visual acuity of at least 20/80. Perceived driving disability (PDD) was assessed by a questionnaire. Subtracting daytime from night-time driving question scores revealed PDD at night (PDDN), subtracting scores of questions for driving in familiar places from those in unfamiliar places revealed PDD at unfamiliar places (PDDU). RESULTS: PDD was strongly related to visual acuity, contrast sensitivity and useful field of view (UFOV). Specific relations existed between PDDN and Nyktotests and Mesotests and between PDDU and UFOV. These associations were enhanced in a subset of subjects with better visual acuities. CONCLUSIONS: Vision screening tests correlate well with perceived driving disabilities, especially when a subtraction method is used in the questionnaire to reveal condition dependent disabilities. Additional tests for visual acuity are useful, especially in subjects with better visual acuity.

[The practice guideline 'Refraction errors' from the Dutch College of General Practitioners: response from the perspective of ophthalmology]. / De standaard 'Refractieafwijkingen' van het Nederlands Huisartsen Genootschap; reactie vanuit de oogheelkunde.

The practice guideline 'Refraction errors' from the Dutch College of General Practitioners provides a guideline for referral of persons aged 6 to 65 with gradual loss of vision to either an optician or an ophthalmologist. In this guideline, relevant questions regarding important symptoms are missing, and the value of the proposed examination employing 'diagnostic refraction' has insufficient scientific support. In addition, the possibility to send children between 6 and 10 years of age to the optician may be dangerous for some of the patients, and there are no explicit indications for the urgency of referral to the ophthalmologist. Due to these short-comings, the guideline may fail to provide optimal preventive and therapeutic eye care for the target group of patients concerned.

Patient satisfaction after corneal transplantation.

PURPOSE: To determine the relationship between objective and subjective outcome measures and patient satisfaction after corneal transplantation. METHODS: Data were collected for 184 patients who underwent a corneal transplantation between 1 and 5 years ago. Only patients with the diagnosis of bullous keratopathy, endothelial decompensation (or Fuchs dystrophy), nonherpetic keratitis, and keratoconus were included. Objective treatment outcome measures, such as clarity of the graft and visual acuity in the grafted eye, were collected prospectively. Visual acuity of the other eye was collected retrospectively by chart review. Subjective outcome measures were derived from a retrospective survey. In addition to assessment of patient satisfaction, the survey provided information regarding subjective outcome measures, such as visual functioning and quality of life. RESULTS: The response rate was 86%. Generally, patients indicated that they were satisfied with the results of the transplantation. Age was negatively related to satisfaction, with older patients being less satisfied. On average, patients with keratoconus were most satisfied. Subjective outcome measures explained 57% of the variance in patient satisfaction, whereas objective factors explained 12%. Receipt of patient education during treatment was the best predictor. Other important variables were quality of life and visual functioning. CONCLUSION: In general, corneal transplantation had a positive effect on objective and subjective outcome measures. Patient satisfaction was better predicted by subjective outcomes than by objective outcomes. Patient education, in particular, proved to be a crucial factor. Objective outcome measures appeared to have a more indirect influence on patient satisfaction.

[Loss of an eye due to hyper-IgE syndrome after corneal transplantation]. / Een verloren oog door het hyper-IgE-syndroom na een hoornvliestransplantatie.

A 37-year-old patient with bilateral keratoconus underwent a perforating cornea transplantation after acute onset of pain and hydrops of the right cornea. One day after operation endophthalmitis developed, caused by a viridans streptococcus. Hyper-IgE syndrome was suspected because of the patient's crude facial features. His medical history brought up additional symptoms of this disease. IgE levels were extremely elevated (7320 kU/l), the eosinophil count was slightly raised (0.25 x 10(9)/l). The patient was treated with several local antibiotics but his vision was only light perception at the time of discharge from the hospital. This case illustrates how an usually successful operation may have a disastrous outcome in case of late diagnosis of the hyper-IgE syndrome. The hyper-IgE syndrome can be recognized by the characteristic facial features in combination with the often extensive (juvenile) medical history with infections, and by elevated serum IgE levels. As patients with the hyper-IgE syndrome are extremely susceptible to develop infections, prophylactic antibiotic therapy is indicated in surgical procedures.

Longitudinal analysis of varicella-zoster virus DNA on the ocular surface associated with herpes zoster ophthalmicus.

PURPOSE: Longitudinal analysis of varicella-zoster virus DNA on the ocular surface of patients with herpes zoster ophthalmicus. METHODS: Clinical specimens were obtained from the bulbar conjunctival surface with a cotton-tipped swab at weekly intervals for 6 consecutive weeks from 21 patients with acute ophthalmic zoster with a skin rash duration of less than 7 days. All patients received oral valacyclovir 1000 mg three times daily for 10 days without additional corticosteroids. The swabs were analyzed by means of polymerase chain reaction for the presence of varicella-zoster virus and herpes simplex virus type 1 DNA. Conjunctival swabs were also obtained from a control group of 20 patients with cataract. RESULTS: On inclusion, varicella-zoster virus DNA was present on the ocular surface of 19 of the 21 patients. Six varicella-zoster virus DNA-positive patients had no signs of ocular inflammation. All control swabs were negative for both varicella-zoster virus and herpes simplex virus DNA. The duration of varicella-zoster virus DNA detection from rash onset varied from 2 to 34 days. The number of days between the onset of herpes zoster skin rash and the latest positive varicella-zoster virus DNA test was significantly longer in patients whose age was equal to or above the median age of 66 years than in the younger patients (Mann-Whitney test: P =.0004). At 6-week follow-up, all conjunctival swabs were negative for varicella-zoster virus DNA. However, at that time, the eyes of seven patients were still inflamed. CONCLUSION: The duration of varicella-zoster virus DNA shedding in herpes zoster ophthalmicus is highly variable and age dependent, and is probably related to the host immune response.

Beneficial effect of HLA-DR matching on the survival of corneal allografts.

BACKGROUND: Although HLA typing and matching have been used for 3 decades, that practice has been poorly implemented in corneal transplantation, mainly because of inconclusive or contradictory analytical results. Consequently, we studied the immune response of corneal transplant recipients to HLA histoincompatibilities in a large homogeneous study. METHODS: All corneal transplantations performed by a single surgeon between 1976 and 1996 were studied. HLA-AB matching was used for recipient selection. All HLA typings were performed by a single experienced laboratory. Population genetic techniques were used to assess the validity of the HLA typings. Mono- and multivariate analyses were performed to identify the factors which significantly influence the survival of corneal allografts. Simulation studies were carried out to demonstrate the effects of mis-typed donor and recipient HLA-DR typings on analytical results. RESULTS: Retransplantation, degree of vascularization, HLA-AB and DR matching, endothelial cell count, graft size, recipient gender, and storage method were identified as significant factors by our monovariate analyses. A Cox proportional hazards survival analysis model identified degree of vascularization and HLA-AB and DR matching as significant prognostic factors when all immunological rejection episodes were used, P=0.000001. When only irreversible immunological rejection episodes were used, panel reactive antibodies, retransplantation, and number of rejection events were also identified, P=0.000001. Simulation studies showed that the effects of HLA-DR matching are abrogated by poor HLA-DR typings. CONCLUSIONS: Corneal allograft recipients have a normal alloimmune response to histoincompatibilities. Demonstration of that fact requires accurate HLA typings.

Risk and prognostic factors of postherpetic neuralgia and focal sensory denervation: a prospective evaluation in acute herpes zoster ophthalmicus.

OBJECTIVES: To determine the general risk and the prognostic factors of postherpetic neuralgia and focal sensory denervation in ophthalmic zoster disease. STUDY DESIGN: A prospective clinical study. SETTING: An ophthalmic practice participating in an eye-care network. PATIENTS: A cohort of 81 immunocompetent adult patients with herpes zoster ophthalmicus and referred by their general practitioner during the acute phase of the disease. METHODS: Various acute phase clinical parameters were determined via patient history and regular ophthalmic examinations. At a 2-month follow-up, the intensity of postherpetic neuralgia, rated on a 4-point verbal scale, and focal sensory denervation was determined. Skin tactile sensation within the ophthalmic dermatomes was tested with use of a cotton-wool tip, and corneal sensitivity was measured with use of a Cochet-Bonnet esthesiometer by comparing each eye. Statistical analysis was performed via chi2 analysis or Fisher exact test to identify prognostic factors of postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. RESULTS: At a 2-month follow-up, pain of varying intensity was reported by 38 participants (47%). Of these patients, 25 patients (31%) rated their pain as mild, 8 patients (10%) rated their pain as moderate pain, and 5 patients (6%) rated their pain as severe. At that time, focal loss of normal skin or corneal sensation was detected in 49 patients (60%). Patient age, acute neuralgia score, manifestation and extent of acute skin rash, signs of ocular inflammation, and nontrigeminal cranial nerve involvement were all associated with prolonged pain and tactile sensory loss. CONCLUSIONS: The severity of acute skin rash, based on a specific manifestation of cutaneous herpes zoster eruptions, and the extent of infection to other neural pathways were clearly associated with postherpetic neuralgia and focal sensory denervation at a 2-month follow-up. These findings suggest that the inability of the immune system to control the spread of replicating varicella-zoster virus in the initial phase of the disease is an important factor in the pathogenesis of chronic zoster-related neuropathy.

Alcaligenes xylosoxidans endophthalmitis 8 months after cataract extraction.

PURPOSE: To report a case of Alcaligenes xylosoxidans endophthalmitis and to increase awareness of its potential as an intraocular pathogen. METHODS: An 80-year-old woman in good general health developed A. xylosoxidans endophthalmitis 8 months after an uncomplicated cataract extraction performed at another institution. Eventually, vitrectomy with removal of the intraocular lens and capsule was performed because of recurrent disease after intravitreal antibiotic injections. RESULTS: Microbiologic examination of the vitreous biopsies and capsule disclosed A. xylosoxidans, a motile, gram-negative rod resistant to many antibiotics. CONCLUSION: A. xylosoxidans should be considered as a cause of low-grade endophthalmitis after cataract surgery.

Are cytokine patterns in aqueous humour useful in distinguishing corneal graft rejection from opacification due to herpetic stromal keratitis?

PURPOSE: Intra-ocular cytokine profiles were determined to study the immunological mechanisms of corneal graft opacification due to rejection and/or herpetic stromal keratitis (HSK). METHODS: Sera and aqueous humour (AH) were sampled shortly after the onset of corneal graft opacification, group I (n=18). In eyes with clear grafts, samples were taken 5 months after transplantation, group II (n=59). Samples of non-inflamed eyes, prior to cataract surgery, were used to determine baseline cytokine levels, group III (n=49). Total protein (TP) levels were measured with Bradford reagent and interleukin (IL)-6, IL-10, IL-4 and interferon (IFN)-gamma with ELISAs. RESULTS: All patients who's corneal grafts showed clinical evidence of graft opacification due to rejection and/or HSK were sampled. In the AH-samples of group I, increased levels of TP were found in 60% (9/15), IL-6 in 79% (11/14), IL-10 in 39% (7/18) and IL-4 in none (0/12). IFN-gamma was detected in 19% (3/16), in the case of HSK only. In contrast, samples obtained from patients with clear grafts in group II showed increased levels of TP in 36% (20/55), IL-6 in 14% (8/57) and IL-10, IL-4 or IFN-gamma in none (n=58). CONCLUSIONS: During corneal graft rejection and/or HSV-infection, increased levels of TP and IL-6 in AH confirmed anterior chamber inflammation with breakdown of the blood-aqueous barrier. Based on the data presented, cytokine patterns in the AH do not appear to distinguish corneal opacification due to graft rejection from that due to herpes keratitis.

Post-corneal transplant tumors of nondonor origin in the anterior chamber of the eye: a case report.

PURPOSE: To investigate whether post-corneal transplant tumors are of donor origin, we studied the case of a 29-year-old female corneal transplant recipient who developed tumors in the anterior chamber on the iris of her right eye 7 years after transplantation. METHODS: Because the corneal graft donor was a 53-year-old man whose cause of death was reported as heart failure but who had uremia secondary to a metastatic Grawitz's tumor, transmission of his malignancy had to be excluded. One of the patient's iris tumors was removed through an incision in the cornea for examination to establish the diagnosis. RESULTS: The histological examination of the iris mass showed the typical picture of a noncaseous epithelioid cell granuloma compatible with the diagnosis of sarcoidosis. The observed post-corneal transplant tumor was clearly not of donor origin. Nevertheless, when tumor growth is observed in an eye after corneal transplantation, transmission of a malignancy has to be excluded. To the best of our knowledge, this is the first report of sarcoidosis with iris nodules after corneal transplantation. CONCLUSION: Our case report illustrates the importance of keeping reliable medical histories of graft donors and of their use in establishing whether post-transplant tumors are of donor origin. The long-term storage of donor medical records should be recommended because of the importance of being able to access that information even years after transplantation.