Course of pattern-reversed visual evoked cortical potentials in 30 eyes after bony orbital decompression in dysthyroid optic neuropathy.

AIM: To investigate optic nerve function using the pattern-reversed visual evoked cortical potentials (VECP) before and after bony orbital decompression in dysthyroid optic neuropathy (DON) due to Graves' disease. METHODS: A total of 30 eyes of 15 patients (n=14 female) were observed over 30 ± 13 months after bony three-wall orbital decompression. We examined visual acuity (VA), VECP P100 amplitudes and latencies, as well as proptosis using Hertel's exophthalmometry. RESULTS: Mean logarithm of the minimum angle of resolution (logMAR) VA increased, statistically significantly, by 2.4 lines during 30 ± 13 months (from 0.38 ± 0.25 before surgery to 0.14 ± 0.1 at the end of observation, p=0.0001). All eyes maintained or improved vision by at least one line. Mean postoperative reduction of proptosis was 6.4 ± 3 mm. While VECP P100 amplitudes improved significantly, P100 latencies remained abnormal in 18 eyes (60%) during follow-up of 10 ± 7 months. Nine eyes (30%) with previous latency defects improved in at least one check test, five of which normalised completely. Worsening was evident in seven eyes (23%), and three previously normal eyes developed new pathological latencies. P100 latencies in 14 eyes (47%) remained unchanged. CONCLUSION: After decompression surgery, DON remission was observed in all patients regarding vision and VECP amplitudes. New or persistent P100 latency defects were seen in 60% of eyes after surgery. DON is considered to be caused by compressive ischaemic damage, which further underlines the importance of early decompression surgery.

[Comparison of superselective intraarterial fibrinolysis with conservative therapy. Use in patients with acute non-arteritic central retinal artery occlusion]. / Vergleich der superselektiven intraarteriellen Fibrinolyse mit konservativer Therapie. Einsatz bei Patienten mit akutem nichtarteriitischem Zentralarterienverschluss.

The results of conservative treatment for central retinal artery occlusion (CRAO) vary considerably and although local intraarterial fibrinolysis (LIF) is a promising treatment, outcomes have not been compared in randomized trials. The prospective randomized multicenter study by the European Assessment Group for Lysis in the Eye (EAGLE) is the first clinical trial to compare treatment outcomes of conservative standard treatment (CST) and LIF for acute non-arteritic CRAO. Patients (age 18-75 years) with CRAO present for less than 20 h and best-corrected visual acuity (BCVA) <0.5 logMAR were randomized to either CST or LIF group. Primary endpoint was BCVA after 1 month and secondary endpoint was safety. Mean BCVA (logMAR) improved significantly in both groups and did not differ between the groups. Because of similar efficacy and the higher rate of adverse events in the LIF group the study was halted after the first interim analysis. Due to the similar outcomes of the two therapies and the higher rate of adverse reactions associated with LIF superselective lysis cannot be recommended for the management of acute CRAO.

[Different indications of photodynamic therapy in ophthalmology]. / Verschiedene Indikationen der photodynamischen Therapie in der Augenheilkunde.

BACKGROUND: Photodynamic therapy (PDT) in eye disease was approved 10 years ago for age-related macular degeneration (AMD). Thereafter it was approved for choroidal neovascularisation (CNV) in pathological myopia. The treatment regimen is based on two prospective, multicentre trials (TAP and VIP studies). MATERIAL AND METHODS: In the meantime PDT has been successfully used also in several other ocular diseases. PDT is minimally invasive and has an excellent side effect profile. Different diseases and their treatment with PDT are discussed. RESULTS: The treatments of idiopathic CNV, secondary CNV in inflammatory diseases of the retina and choroid, choroidal haemangioma, vasoproliferative tumours, malignant melanoma of the choroid, and central serous chorioretinopathy with PDT are described. In most patients the disease progression can be stopped and in some the PDT treatment results in visual improvement. The prognosis is better in patients with early disease detection and small lesions. CONCLUSION: Several retinal and choroidal diseases can be treated successfully with PDT. Except for AMD and pathological myopia, PDT is an off label treatment.

Photodynamic therapy with verteporfin in paediatric and young adult patients: long-term treatment results of choroidal neovascularisations.

BACKGROUND: Vision impairment in children and young adults may derive from choroidal neovascularisation (CNV) related to numerous conditions. The aim of this study is to highlight the applicability of photodynamic therapy using verteporfin (PDT) in these patients. METHODS: In 16 eyes of 16 consecutive patients aged 30 years or younger, prospective open-label PDT was performed. Outcomes of visual acuity as well as changes in CNV lesion parameters were evaluated. RESULTS: The mean patient age at first PDT was 19.7 (SD 8.7) years (range 6-30). 81% of the patients retained stable vision within two lines or exceedingly improved vision during follow-up of 34 (24) months. Significant vision gain was denoted in seven paediatric patients (2.7 (1.4) lines, mean (SD); p = 0.019) as well as in a subgroup of 12 patients not affected by active uveitis (2.6 (2.0) lines, p = 0.0005). Two patients with multifocal choroiditis and panuveitis (MCP) experienced vision losses of five and 11 lines after four PDT sessions despite receiving additional steroidal treatment. Except for one patient with MCP and two patients who dismissed follow-up, a mean of 2.2 (1.3) PDTs per patient sufficiently inactivated CNV lesions during follow-up. In the area of the former PDT spot, alterations of the pigment epithelium increased by 40% without correlation to changes in vision. CONCLUSIONS: The results indicate good PDT efficacy and tolerability most promising in a subgroup of patients with vision-impairing CNV not associated with active uveitis. PDT in young patients with CNV remains a valuable treatment with good risk-benefit profile over the long term.

[Lysis therapy vs. conservative therapy: randomised and prospective study on the treatment of acute central retinal artery occlusion (EAGLE study)]. / Lysetherapie vs. konservative Therapie: Randomisierte und prospektive Studie zur Behandlung des akuten Zentralarterienverschlusses (EAGLE-Studie).

In the prospective, randomised and multicenter EAGLE study, the therapeutic efficiency of local intra-arterial fibrinolysis (LIF) versus conservative treatment is being tested in patients with an acute central retinal artery occlusion (CRAO). The most important inclusion criteria are: (1) age between 18-75 years, (2) CRAO not older than 20 h, and (3) visual acuity <0.32. The primary study endpoint is the visual acuity before and 1 month after therapy. The study was started in 2002. To August 2006, 63 of the 200 required patients have been included in the study at 17 medical centers in Germany, Switzerland and Austria.

[Endoresection of large uveal melanomas after pretreatment by single-dose stereotactic convergence irradiation with the leksell gamma knife--first experience on 46 cases]. / Endoresektion grosser Melanome der Uvea nach stereotaktischer Single-dose-Vorbestrahlung mit dem Leksell Gamma-Knife -- Erste Erfahrungen an 46 Fällen.

BACKGROUND: The aim of this non-comparative, consecutive case series is to evaluate the short-term results after endoresection of large uveal melanomas in combination with pretreatment with stereotactic gamma knife radiosurgery. METHODS: Between March 2000 and November 2002, forty-six patients with large uveal melanomas underwent stereotactic radiosurgery followed by endoresection of the tumour via a standard three-port vitrectomy including laser photocoagulation and silicone oil tamponade. The average tumour height was 9.5 mm. The minimum dose delivered to the tumour volume was 25 Gy. RESULTS: The median follow-up time was 410 days. In 40 cases (87 %), the eye was retained with a VA of 20/200 or better in 30 cases (65.2 %) and 20/63 or better in ten cases (21.7 %). In 12 eyes with a follow-up of >/= 0.5 years, the median VA was 20/80 after silicone oil removal and cataract surgery had been performed. Six eyes (13 %) were enucleated due to serious complications caused by the radiosurgery (3 cases) or endoresection (3 cases). In 13 patients (28.2 %), additional major surgery was required. Seven patients developed liver metastases during follow-up and six patients died. No local tumour recurrences were observed. CONCLUSIONS: Eyes with large uveal melanomas can be salvaged by stereotactic radiotherapy followed by endoresection.

Ruthenium-106 plaque brachytherapy for symptomatic vasoproliferative tumours of the retina.

AIM: To investigate the safety and efficacy of beta ray brachytherapy in treatment of vasoproliferative tumours of the retina (VTR). METHODS: 35 consecutive patients with symptomatic VTR were treated with a ruthenium-106 ((106)Ru) plaque. Three tumours had been treated previously (two with cryotherapy; one with transpupillary thermotherapy). 32 VTR (91.4%) were located in the lower half of the retina and all of them were found between the mid-periphery and the ora serrata. The mean tumour thickness was 2.8 mm. An exudative retinal detachment was present in 25 eyes (71.4%) and in 15 cases (42.9%) hard exudates were found in the macula. The major symptom was loss of vision (77.1%). RESULTS: Brachytherapy was well tolerated by every patient. The mean applied dose was 416 Gy at the sclera and 108 Gy at the tumour apex. In all but four eyes (88.6%), it was possible to control the VTR activity. The median follow up time was 24 months. Three of the above mentioned four eyes with treatment failure had had secondary glaucoma before therapy. There was no case of radiation induced neuropathy or retinopathy. Cataract surgery was necessary for five patients. The development of epiretinal gliosis was the most common event during follow up (n = 10, 28.6%). The mean visual acuity decreased slightly (0.33 before and 0.29 after brachytherapy). Multivariate analysis showed that the presence of macular pathology before treatment was associated with a 6.1-fold risk of vision of 0.25 or better (p = 0.03). CONCLUSIONS: beta ray brachytherapy with (1106)Ru plaques was able to control the activity of VTR and retain vision. Cases with secondary glaucoma before treatment had a very poor prognosis.

Multicenter study of the European Assessment Group for Lysis in the Eye (EAGLE) for the treatment of central retinal artery occlusion: design issues and implications. EAGLE Study report no. 1 : EAGLE Study report no. 1.

BACKGROUND: The natural course of central retinal artery occlusion (CRAO) often leads to legal blindness in the affected eye. To date, none of the conservative therapies had proven effective in retrospective studies. In 1991, a new minimally invasive therapy was started in patients with an acute CRAO. This therapy, namely, local intra-arterial fibrinolysis, is comparable to the minimally invasive therapy in patients with an acute ischemic stroke. In pilot studies, it showed promising results in comparison with conservative treatments. The efficacy of this method is now being investigated in a randomized multicenter study. METHODS: The European Assessment Group for Lysis in the Eye (EAGLE) started a prospective and randomized multicenter study in 2002 to evaluate therapeutic efficacy. Inclusion criteria are age between 18 and 75 years and a CRAO not older than 20 h with a visual acuity less than 0.32. The most important exclusion criteria are branch retinal artery occlusion (BRAO), cilioretinal arteries supplying the macula, and serious general disease. After randomization the patient is treated by conservative or local intra-arterial lysis therapy. The conservative regime included bulbus massage, lowering intraocular pressure with topical beta-blocker and acetazolamide, acetylsalicylic acid, heparin, and-depending on the hematocrit-isovolemic hemodilution. In case of local intra-arterial fibrinolysis, a maximum of 50 mg rtPA is injected into the ophthalmic artery by the neuroradiologist. During the following 5 days, all patients are treated with heparin. Primary study end point is visual acuity 1 month after therapy in comparison with visual acuity before therapy. The calculated sample size is 100 patients per subtrial (a total of 200 patients). The study was started in June 2002. To April 2005, 47 patients were included. CONCLUSIONS: The EAGLE Study is the first randomized prospective clinical trial to compare conservative medical treatment and local intra-arterial fibrinolysis in patients with CRAO. The results of this study should enable ophthalmologists and neuroradiologists to improve the therapy of patients with acute CRAO. To April 2005, treatment is only justified in randomized multicenter studies because of the limited therapeutical visual outcome. We welcome new study centers to join.

Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma.

AIM: To investigate the safety and efficacy of photodynamic therapy with verteporfin in patients with choroidal haemangioma. METHODS: A non-randomised, prospective clinical investigation of 19 patients with symptomatic circumscribed choroidal haemangioma was performed. Unsuccessful pretreatment (external beam irradiation, laser photocoagulation) was performed in four patients. Patients were included when (1) subretinal exudation involving the fovea, (2) a decrease in visual function, and (3) additional symptoms (for example, metamorphopsia) were present. Photodynamic therapy (PDT) was performed with verteporfin at a concentration of 6 mg/m(2) body surface area and a light dose of 100 J/cm(2) at 692 nm. RESULTS: The mean follow up time was 10.6 months (2-24 months). The mean number of treatment sessions was 2.15 (range 1-5). Visual acuity improved by at least one line in 73.3%, by at least two lines in 42.1%, was stable in 21.1%, and decreased by one line in 5.2% of the patients. Exudation was completely resolved in 94.8% of the cases. Regression of tumour height was documented in all 19 tumours. Patients receiving any pretreatment before PDT, a visual acuity of 0.1 and less, a history of more than 30 months, and no significant response after the first PDT session, did not show any significant improvement. Cox regression analysis revealed that the number of PDT treatment sessions was inversely associated with the improvement in visual acuity of at least two lines. No recurrences and no local or systemic side effects were observed during the follow up time. CONCLUSION: PDT using verteporfin is a safe and effective therapy for the treatment of symptomatic choroidal haemangioma even in tumours located beneath the fovea.

Monitoring retinal function in neovascular maculopathy using multifocal electroretinography - early and long-term correlation with clinical findings.

PURPOSE: To objectively investigate and longitudinally monitor retinal function in patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD) and myopia using multifocal electroretinography (mfERG). METHODS: Patients with classic and occult subfoveal CNV secondary either to AMD or to myopia were enrolled in the study. The mfERGs were performed at the beginning of the study and every 3 months subsequently during a follow-up period of 15 months. In addition, standardized visual acuity testing, ophthalmologic examinations, color fundus photographs and fluorescein angiography were performed. The mfERG records were derived with the VERIS-System (Electro-Diagnostic Imaging, San Mateo, Calif., USA); 103 locations within the central 50 degrees in diameter were stimulated concurrently by means of the m-sequence technique. Fixation stability was monitored throughout the recording session with an infrared eye monitoring system (VERIS Refractor/Camera unit). The first-order response component was extracted for each stimulated retinal location. The response densities of the first-order kernel were evaluated as a function of eccentricity from the center (ring 1) to the periphery of the stimulated area (ring 6). The results were compared to those derived from age-matched normal control groups. For each patient mfERG responses measured on follow-up visits were compared to each other to evaluate and monitor changes in retinal function. These changes were tested for correlation with those observed in other clinical and electroretinographic findings. Statistical analysis was performed using the Pearson coefficient. RESULTS: Subfoveal neovascular maculopathy was associated with a reduction in response density most prominent within the central 5 degrees over the area affected by CNV detected either at the beginning of the study or at the follow-up recordings. During the follow-up period patients 1 and 4 showed stabilization or a slight increase in response densities over the neovascular lesion-complex and a corresponding stabilization or slight increase in visual acuity accompanied by a decrease in the activity of the neovascular lesion as determined by fluorescein angiography. Patient 2 revealed an increase in response density correlating with an increase in visual acuity and decrease in lesion size. In the contralateral eye of this patient the response density dropped in the area of new subfoveal CNV. In patient 3 continuous progression of the disease was documented by fluorescein angiography and visual acuity. It correlated well with a continuous decrease in retinal response densities during the follow-up. CONCLUSIONS: Objective monitoring of retinal function and correlation with morphological and psychophysical findings was at least in part possible in patients suffering from AMD and myopia. In all of four patients whose subfoveal CNV was documented by fluorescein angiography. Response densities were reduced particularly in the central 5 degrees and in visual acuity. The mfERG data showed a moderate to high statistical correlation with visual function as measured by visual acuity. On the other hand, the greatest linear dimension of the lesion size showed only a weak to moderate statistical correlation with both the response densities of the mfERG and the visual acuity. We conclude that the size of the CNV complex does not represent an accurate measure of retinal function in neovascular maculopathy. The good correlation of the mfERG data with visual acuity suggests that it may serve for objective assessment of retinal function, of the areas overlying the CNV. It shows potential as a valuable tool for longitudinal monitoring of AMD patients.

[Corneoretinal dystrophy (Bietti)-- Long-term course of one patient over a period of 30 years, and interindividual variability of clinical and electrophysiological findings in two patients]. / Kristalline korneoretinale Dystrophie (Bietti) - Langzeitverlauf von einem Patienten von 30 Jahren und interindividuelle Variabilität klinischer und elektrophysiologischer Befunde von zwei Patienten12.

BACKGROUND: A tapetoretinal dystrophy with crystalline deposits of the retina and limbal cornea was described by Bietti in 1937. To date, only a few cases with long-term follow up have been reported. PATIENTS AND METHODS: Two patients are presented including the clinical findings, fluorescein angiography, electrophysiology [electroretinography (ERG); electrooculography (EOG), multifocal electroretinography (MERG)], adaptometry, and transmission electron microscopy (TEM) of peripheral blood lymphocytes. The clinical findings were at least in part documented over a period of 30 years. RESULTS: The most striking features were deposits in the retina and cornea associated with crystalloid lysosomal inclusions in peripheral lymphocytes, and choroidal atrophy especially in advanced stages of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), the responses of the MERG and visual fields were affected progressively during the course. These advanced changes of the retinal pigment epithelium and choriocapillaris were observed in the 2(nd) decade already. CONCLUSIONS: The findings of deposits in the cornea, retina and lymphocytes may help to differentiate BCD from other chorioretinal dystrophies. The results confirm a variable course in clinical expression of BCD between individuals.

CNGA3 mutations in hereditary cone photoreceptor disorders.

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.

OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance.

We and others have shown recently that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein cause autosomal dominant optic atrophy (ADOA) linked to chromosome 3q28-q29. Here we report screening of the OPA1 gene in a sample of 78 independent ADOA families. OPA1 mutations were identified in 25 patients (detection rate 32.1%) including 16 novel mutations. We successfully amplified OPA1 cDNA prepared from leukocyte RNA of three patients, and found the amount of transcripts harboring the Arg366Stop mutation was significantly reduced compared with transcripts derived from the normal chromosome. Analysis of the distribution of OPA1 mutations in ADOA revealed that most missense mutations cluster within the putative GTPase domain, and that there is a preponderance of mutations, which result in premature translation termination. These observations support the notion that haploinsufficiency may represent a major pathomechanism for ADOA. In addition, we identified an ADOA patient who is a compound heterozygote for two OPA1 missense mutations. The fact that this patient is by far more severely affected than her simple heterozygotic parents and siblings implies that at least these OPA1 alleles behave semi-dominantly rather than purely dominantly. Clinical examination revealed considerable variability in disease expression among patients carrying OPA1 mutations and no strict correlation with either the position or the type of mutation.

Leber congenital amaurosis and retinitis pigmentosa with Coats-like exudative vasculopathy are associated with mutations in the crumbs homologue 1 (CRB1) gene.

Mutations in the crumbs homologue 1 (CRB1) gene cause a specific form of retinitis pigmentosa (RP) that is designated "RP12" and is characterized by a preserved para-arteriolar retinal pigment epithelium (PPRPE) and by severe loss of vision at age <20 years. Because of the early onset of disease in patients who have RP with PPRPE, we considered CRB1 to be a good candidate gene for Leber congenital amaurosis (LCA). Mutations were detected in 7 (13%) of 52 patients with LCA from the Netherlands, Germany, and the United States. In addition, CRB1 mutations were detected in five of nine patients who had RP with Coats-like exudative vasculopathy, a relatively rare complication of RP that may progress to partial or total retinal detachment. Given that four of five patients had developed the complication in one eye and that not all siblings with RP have the complication, CRB1 mutations should be considered an important risk factor for the Coats-like reaction, although its development may require additional genetic or environmental factors. Although no clear-cut genotype-phenotype correlation could be established, patients with LCA, which is the most severe retinal dystrophy, carry null alleles more frequently than do patients with RP. Our findings suggest that CRB1 mutations are a frequent cause of LCA and are strongly associated with the development of Coats-like exudative vasculopathy in patients with RP.

[Clinical findings in autosomal recessive syndrome of blue cone hypersensitivity]. / Klinische Befunde bei autosomal-rezessivem Syndrom der Blauzapfenhypersensitivität.

BACKGROUND: Intrafamilial variability of the syndrome of night blindness, maculopathy, and enhanced S-cone hypersensitivity was examined. PATIENTS AND METHODS: Siblings with a history of night blindness and reduced visual acuity were examined clinically, psychophysically, electroretinographically (ERG), and electro-oculographically (EOG). RESULTS: The siblings had had night blindness since early childhood and reduced visual acuity since the age of 20 years. Ophthalmoscopy showed degenerative, pigmented changes and subretinal spots, while one sibling had cystic lesions in the fovea. Scotopic ERG showed no rod-driven responses, while large, slow waveforms were detected in response to bright flashes. Photopic ERG induced responses similar in time, amplitude, and configuration to those of the dark-adapted ERG. The b-wave configuration was unchanged in response to chromatic stimuli. However, photopic ERG was more sensitive to blue and white than to red stimuli. The light peak on EOG was reduced. CONCLUSIONS: The enhanced S-cone sensitivity syndrome was expressed to a different degree of severity and probably inherited in an autosomal recessive mode. These unusual ERG findings may be due to a depressed rod system and an increased number of S-cone photoreceptors, postreceptoral circuits, and S-cone sensitive ganglion cells.

[Effect of retinal coagulation status on oxidative metabolite and VEGF in 208 patients with proliferative diabetic retinopathy]. / Einfluss des retinalen Koagulationsstatus auf oxidative Metabolite und VEGF bei 208 Patienten mit proliferativer diabetischer Retinopathie.

BACKGROUND: Oxidative metabolites and different cytokines are believed to be involved in the pathogenesis of (proliferative) diabetic retinopathy. It was the aim of this study to analyze vitreous body and proliferations of diabetic patients for oxidative metabolites and VEGF und to correlate these values to the retinal coagulation status. PATIENTS AND METHODS: The study was performed in 208 patients vitrectomized for diabetic retinopathy (Type I: n = 114, Type II: n = 94). Grouping of patients was performed according to retinal coagulations status: (1) no or minimal preoperative coagulation [mean coagulation area, CA: 156 mm2], (2) coagulation (scatter laser coagulation und/oder cryopexy) < 3 months before surgery [CA: 589 mm2]. (3) coagulation > 3 months before surgery [CA: 546 mm2]. In the vitreous body and, if present, in the fibrovascular proliferations (Type I: n = 83; Type II: n = 73) the level of lipid peroxides (LPO, measured with two methods) and VEGF was determined. RESULTS: In the vitreous body LPO in group 1 were significantly (P < 0.01 (Type I und II)) higher as compared to other groups. In group 3 LPO were significantly lower as compared to group 2 (P < 0.01 (Typ I) and P < 0.05 (Typ II)). Similar results were observed in the proliferations. In Type I patients VEGF values were significantly (P < 0.01 for group 1 vs. 2 and groups 1/2 vs. 3) reduced following coagulation and coagulation + 3 months. In Type II patients only group 3 was significantly (P < 0.01) different from group 1. In proliferations groups 2 and 3 were significantly different from group 1 (P < 0.05 for Typ I and Type II patients). CONCLUSIONS: The time course of the values leads to the conclusion that oxidative metabolites are able to directly modulate growth activity and to exert this effect via induction of VEGF. This hypothesis has to be confirmed in vitro and by means of a prospective study.

EFEMP1 is not associated with sporadic early onset drusen.

The early onset of multiple drusen in the posterior pole of the retina is characteristic of a group of macular dystrophies often referred to as dominant or radial drusen. At least two forms, Doyne honeycomb retinal dystrophy (DHRD) and Malattia Leventinese (MLVT), are associated with a single missense mutation (R345W) in the gene encoding the EGF-containing fibulin-like extracellular matrix protein-1 (EFEMP1) and are now thought to represent a single entity. Here, we present a further evaluation of the role of EFEMP1 in the pathogenesis of sporadic forms of early onset drusen. We analyzed all coding exons of the EFEMP1 gene by SSCP analysis in 14 unrelated individuals with early onset of multiple drusen and no apparent family history of the disease. In this patient group, we did not detect the R345W mutation or any other disease-associated mutation. Three different polymorphisms and two intragenic polymorphic repeats were present in similar frequencies in the patients and control individuals. We conclude that EFEMP1 is unlikely to be involved in the disease in this patient group. This suggests that mutations in a different as yet unknown gene or genes may lead to the early onset drusen phenotype.