Leila Laatikainen

Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial

BACKGROUND Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus. METHODS The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. FINDINGS Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022). INTERPRETATION Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.

Risk Factors of Age-related Maculopathy in a Population 70 Years of Age or Older

PURPOSE To evaluate possible risk factors for age-related maculopathy (ARM) in an epidemiologic cross-sectional population study of inhabitants 70 years of age or older in a rural area in Oulu County, Northern Finland. METHODS Five hundred of the 560 (89 percent) eligible subjects were examined. The diagnosis of ARM was based on fundus photographs in 83 percent of the population or on ophthalmoscopic findings in 13 percent; in 4 percent, the fundi could not be seen. Both early and late forms of ARM were included. RESULTS The prevalence of ARM increased steadily with age without overall significant difference between men and women. The condition was, however, related to high body mass index in men. The ARM appeared to be also associated with the presence of cataract, broad peripapillary atrophy, and severe sclerosis of the retinal arteries, but after controlling for age, these associations were nonsignificant. No association was found between ARM and systemic hypertension, diabetes, smoking, working outside, myopia, glaucoma, or the presence of exfoliation. In logistic regression analysis, age was the only statistically significant risk factor for ARM in both sexes. In men, a high body mass index also was found to be a predictor for ARM. CONCLUSIONS The presence of ARM was associated with cataract and signs of age-related vascular changes in the eyes. Of the general factors, age in both sexes and high body mass index in men were found to be the only predictors of ARM.

Implantable contact lens for high myopia

Purpose: To evaluate the efficacy, safety, and biocompatibility of a collagen polymer implantable contact lens (ICL) (Staar Collamer) as a posterior chamber phakic intraocular lens (IOL) to correct high myopia. Setting: Departments of Ophthalmology, Helsinki University Central Hospital, Helsinki, and Tampere University Hospital, Tampere, Finland. Methods: A Staar Collamer posterior chamber phakic IOL was implanted in 38 eyes of 22 patients with a mean age of 39 years (range 24 to 54 years). The mean preoperative myopia was −15.10 diopters (D) (range −7.75 to −29.00 D). Surgical implantation was performed through a 3.0 mm clear corneal sutureless incision using paraocular anesthesia. The patients were followed clinically up to 3 years. The mean follow‐up was 13.6 months (range 6 to 24 months) for refractive data and 22.3 months (range 6 to 35 months) for complications. The possible inflammatory response to the ICL was measured using a laser flare meter in 12 eyes. Results: Postoperatively, all eyes had a significant increase in uncorrected visual acuity, allowing all but 3 patients (5 eyes) to manage most activities without spectacles. The mean spherical equivalent refraction at the last examination was −2.00 D ± 2.48 (SD) (range +0.13 to −13.00 D), within ±1.00 D of the targeted refraction in 31 eyes (81.6%) and within ±0.50 D in 27 eyes (71.1%). In eyes in which the preoperative myopia was less than −18.00 D (n = 28), the achieved refraction was within ±1.00 D of the intended refraction in 27 eyes (96.4%) and within ±0.50 D in 24 eyes (85.7%). The refraction remained stable with a statistically insignificant change (P > .05) at each interval during the follow‐up. The best corrected visual acuity (BCVA) improved by 1 or more lines in 23 of 32 eyes (71.9%) at 1 year. Two eyes (6.3%) lost 1 line of BCVA. Laser flare photometry showed normal aqueous flare values (11.71 ± 6.61 photon counts/ms) in the 12 eyes measured at least 6 months after ICL implantation. Pupillary block glaucoma requiring surgical intervention occurred in 3 patients (7.9%). One patient (2.6%) developed cataract 1.5 years after ICL implantation; both ICLs were removed, and the refractive errors were corrected by lensectomy and implantation of low‐power posterior chamber IOLs. One patient (2.6%) showed progression of dry macular degeneration at 17 months. Conclusion: At 1 year, ICL implantation had good visual and refractive results with excellent biocompatibility. Long‐term follow‐up is required to confirm that significant complications do not occur in most patients over time.

Prevalence and risk factors of lens opacities in the elderly in Finland. A population-based study.

PURPOSE The distribution and prevalence of lens opacities and visual impairment caused by cataract were studied in an epidemiologic cross-sectional population study of inhabitants 70 years of age or older in three communities in Oulu County, Finland. METHODS Of the 560 eligible subjects, 500 (89.3%) were examined. The best-corrected visual acuity for distance in both eyes was determined. The diagnosis of lens opacities was based on clinical biomicroscopy. The findings were compared with standardized photographs of the Lens Opacities Classification System II. RESULTS One hundred sixty-five (33.0%) persons in the study population had a clear lens in both eyes. Cataract, aphakia, or pseudophakia was recorded in one or both of the eyes in 64.4% (322 persons) of the participants. The prevalence increased with age from 44.6% of persons (n = 88) in the 70- to 74-year-old age group to 97.6% of persons (n = 41) in the 85- to 89-year-old age group. A total of 56.4% of persons had cataract, aphakia, or pseudophakia in both eyes. Nuclear, cortical, and posterior subcapsular opacities were detected in 38.5%, 37.6%, and 27.7% of the participants, respectively. Exfoliation was present in one or both eyes in 22.1% of the participants. There was no difference in the prevalence of cataract between the sexes when age was considered. Visual impairment to 20/50 or worse was at least partly due to cataract in 23.8% of the right eyes and 22.4% of the left eyes. Significant risk factors for cataract were age and the presence of exfoliation in men and age, occupational exposure to sunlight, and current cigarette smoking in women. CONCLUSIONS Almost two thirds of the population 70 years of age or older had lens opacities, and in 23.1% of the eyes visual impairment to 20/50 or worse was at least partly due to cataract. Including the patients who had undergone surgery, 30.3% of all the eyes of persons 70 years of age or older can be considered for cataract surgery.

REFRACTIVE ERRORS AND OTHER OCULAR FINDINGS IN SCHOOL CHILDREN

A series consisting of 411 non‐selected school children, 7 to 15 years of age, was examined. Decreased visual acuity (less than 0.8 in one or both eyes without correction) was found in 55 children (13.4%), the frequency increasing from 3.7% to 29.1% with age. The frequency of hyperopic eyes (+2.0 D. or more) decreased from 19.1% to 3.6% and the frequency of myopic eyes (‐0.5 D. or more) increased from 1.9% to 21.8% with age. Altogether, myopia, hyperopia, or astigmatism (1 D. or more) in one or both eyes was found in 93 children (22.6%).

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4

Summary To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29 %) died during the follow-up period; the majority of whom (68 %) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1 c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39 %, p = 0.048) and of parietal cell antibodies (5 vs 14 %, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16 %, p = 0.002), neuropathy (57 vs 23 %, p < 0.001), microalbuminuria (45 vs 6 %, p < 0.0001), coronary heart disease (50 vs 13 %, p < 0.0001), and peripheral vascular disease (27 vs 9 %, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1 c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease. [Diabetologia (1998) 41: 1253–1262]

Quality of vision after AMO Array multifocal intraocular lens implantation.

Purpose: To evaluate safety and efficacy of Array® SA40N multifocal intraocular lens (IOL) (AMO) implantation in cataract surgery. Setting: Helsinki University Eye Hospital, Helsinki, Finland. Methods: In this prospective randomized comparative trial, 80 patients scheduled for cataract surgery were selected based on preoperative counseling and randomized to have multifocal or monofocal IOL implantation. Fifty‐three eyes of 35 patients received a multifocal IOL and 67 eyes of 40 patients, a monofocal IOL. The incidence of complications and visual outcome in the multifocal and monofocal IOL groups were compared. Quality of vision was measured by comparing the severity of visual symptoms (glare, halos, and cataract symptoms score), changes in functional impairment measured by a 7‐item visual function test (VF‐7), changes in global measures of vision (trouble and satisfaction with vision), and range of accommodation and contrast sensitivity. Results: Intraoperative and postoperative complications and adverse events were few and required no further surgical intervention. Both distance and near visual acuities were significantly better in the multifocal group than in the monofocal group; the difference was most prominent in distance corrected near acuity (P<.001). Thirty‐five eyes (67.3%) in the multifocal group and 10 eyes (14.9%) in the monofocal group achieved a distance corrected near acuity of J6 (20/40) or better; 30 eyes (56.6%) and 19 eyes (28.4%), respectively, achieved a best corrected distance acuity of 20/20 or better. Glare symptoms decreased postoperatively in both groups but were slightly more common in the multifocal group. In contrast, halos were significantly more common at 1 month in the multifocal group (P<.001). Contrast sensitivity values were slightly lower with multifocal IOLs at almost all spatial frequencies, but the difference was not significant. The change in the quality of life postoperatively, measured with the VF‐7, was significant and identical in both groups. Conclusions: Pseudophakic eyes with multifocal IOLs had better distance and near acuity and range of accommodation than eyes with a monofocal IOL. Slightly lower contrast sensitivity and increased perception of halos by subjects with the multifocal IOL appear to be an acceptable compromise to enhanced near and distance vision.

Exfoliation Syndrome and Cataract Extraction

In a prospective study of 351 consecutive cataract operations performed on Finnish patients, the prevalence of exfoliation syndrome was 31% (108 of 351 eyes), increasing from 0% (zero of 54 eyes) in patients younger than 60 years to 15% (12 of 78 eyes) in patients aged 60 to 69 years, 42% (57 of 137 eyes) in patients aged 70 to 79 years, and 48% (39 of 82 eyes) in those aged 80 years or more, than has previously been reported in general populations of the same age in Finland. Exfoliation syndrome was more common in patients aged 70 years or more. Glaucoma was found in 41 of 108 eyes with exfoliation syndrome (38%). Exfoliation syndrome increased the risk of intraoperative complications in extracapsular cataract extraction either directly (rupture of the zonules) or through poor dilation of the pupil (rupture of the posterior lens capsule). The occurrence of vitreous loss was fourfold, and the need to use an anterior chamber intraocular lens instead of a posterior chamber lens because of loss of capsular support was tenfold in eyes with exfoliation as compared to those without exfoliation.

Matrix metalloproteinase‐2 (MMP‐2) immunoreactive protein—a new prognostic marker in uveal melanoma?

Uveal melanoma is the most common primary intraocular tumour. Once haematogenous metastasis has occurred, there is no cure for the disease and there is an obvious need for new biological prognostic markers to estimate the risk of metastasis. In this study, the expression of matrix metalloproteinase‐2 (MMP‐2) was characterized immunohistochemically in 29 human uveal melanomas. Enzyme‐linked immunoassays and gelatin zymographies were assessed in order to quantify the expression of gelatinases A and B, as well as the tissue inhibitor of metalloproteinases (TIMPs), in the vitreous body. A total of 49 per cent of the uveal melanomas displayed a positive immunoreaction for MMP‐2 in melanoma cells, the epithelioid cells showing the most frequent staining. There was no correlation between the positivity of MMP‐2 staining and the size of the primary tumour, gender or age. The expression of MMP‐2 was associated with a dismal prognosis: the 5‐year overall survival rate for MMP‐2‐positive cases was significantly inferior to that of the MMP‐2 negative cases, 49 per cent vs. 86 per cent, respectively (p=0·02). A patient group at high risk of metastatic disease was identified; only 38 per cent of patients with a MMP‐2‐positive non‐spindle cell uveal melanoma survived for 5 years. The analyses of MMPs or TIMPs in the vitreous body had no prognostic value. Positive immunostaining for MMP‐2 was observed in the retinal pigment epithelium, corneal epithelium, and fibroblasts in the ciliary body and choroid. It is concluded that immunohistochemical analysis of MMP‐2 may help to predict a risk of metastasis in uveal melanoma. Copyright

Epidemiology of rhegmatogenous retinal detachment in a Finnish population

Abstract. During a ‐4 year period, 1978–1981, 310 eyes of 301 patients living in the district of the Helsinki University Central Hospital were examined for rhegmatogenous detachment of the retina. This corresponds to an annual incidence of 6.9 per 100 000 mean population. The mean age of the patients was 54.2 years, and the sex distribution corresponded with that in the general population. The right eye was significantly (P < 0.05) more often affected than the left eye. 78% of the eyes were phakic, and 22% were aphakic. The corresponding annual incidences were 5.4 for phakic and 1.5 for aphakic detachment per 100 000 mean population. Myopia was found in 51% of the phakic and in 24% of the aphakic eyes. The estimated annual incidence of rhegmatogenous detachment in the myopic population was more than 3 times that in the non‐myopic population. The annual incidence of traumatic rhegmatogenous retinal detachment was 0.8 per 100 000 mean population. There were significant (P < 0.005) seasonal variations in the occurrence of retinal detachment.