[Unmet research and developmental needs in ophthalmology : A consensus-based road map of the European Vision Institute for 2019-2025]. / Forschungs- und Entwicklungsbedarf in der Augenheilkunde ("Unmet needs") : Ein konsensbasierter Fahrplan des European Vision Institute (EVI) für die Jahre 2019 bis 2025.

PURPOSE: To define unmet needs in ophthalmology which can realistically be addressed in the next years (2019-2025) and to describe potential avenues for research to address these challenges. METHODS: Outcomes of a consensus process within the European Vision Institute (EVI, Brussels) are outlined. Disease areas which are discussed comprise glaucoma, retinal dystrophies, diabetic retinopathy, dry eye disease, corneal diseases, cataract and refractive surgery. RESULTS: Unmet needs in the mentioned disease areas are discussed and realistically achievable research projects outlined. CONCLUSION: Considerable progress can be made in the field of ophthalmology and patient-relevant outcomes in the near future.

New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel.

The current standard therapy for patients with diabetic macular oedema (DME)--focal/grid laser photocoagulation--usually does not improve impaired vision, and many patients lose vision despite laser therapy. Recent approval of ranibizumab by the European Medicines Agency to treat visual impairment due to DME fulfils the previously unmet medical need for a treatment that can improve visual acuity (VA) in these patients. We reviewed 1- and 2-year clinical trial findings for ranibizumab used as treatment for DME to formulate evidence-based treatment recommendations in the context of this new therapy. DME with or without visual impairment should be considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy Study (ETDRS) criteria for clinically significant oedema. For DME with centre involvement and associated vision loss due to DME, monthly ranibizumab monotherapy with treatment interruption and re-initiation based on VA stability is recommended. Laser therapy based on ETDRS guidelines is recommended for other forms of clinically significant DME without centre involvement or when no vision loss has occurred, despite centre involvement. Because these recommendations are based on randomised controlled trials of 1-2 years duration, guidance may need updating as long-term ranibizumab data become available and as additional therapeutic agents are assessed in clinical trials.

Central retinal thickness measured with HD-OCT shows a weak correlation with visual acuity in eyes with CSME.

AIMS: To investigate the correlation between increased retinal thickness (RT) measured with spectral domain high-definition optical coherence tomography (OCT) (Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, California, USA)) and best-corrected visual acuity (BCVA) in eyes with clinically significant macular oedema (CSME) and type 2 diabetes. METHODS: Seventy eyes with CSME were included in this observational study. Sixty-two eyes were considered for analysis and were classified as having/not having retinal thickening in the central fovea (central 500-microm-diameter circle) by Cirrus HD-OCT. RT measurements were computed and correlated with BCVA. For comparison purposes, the Stratus OCT (Carl Zeiss Meditec, Dublin, California, USA) central point thickness was also obtained in these eyes. RESULTS: In the 19 eyes with CMSE identified by Cirrus HD-OCT without increased RT in the central fovea (500-microm-diameter circle), no correlation was found between RT and BCVA (R=0.062; 95% CI -0.404 to 0.502). In the 43 eyes where the Cirrus HD-OCT identified an increased RT in the central fovea (central 500-microm-diameter circle), only a moderate correlation between RT and BCVA was found (R=-0.459; 95% CI -0.667 to -0.184). CONCLUSION: Correlations between RT and BCVA in CSME are only present when the central 500-microm-diameter circle is involved. However, even in this circumstance, a correlation was found in only 48.8% of the cases. RT cannot, therefore, be used as a surrogate outcome for visual acuity changes.

Prospective randomised controlled trial comparing sub-threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema.

AIM: The study was a prospective randomised controlled double-masked trial performed in two centres to compare sub-threshold micropulse diode laser photocoagulation (MPDL) with conventional green laser photocoagulation (CGL) in the treatment of clinically significant diabetic macular oedema (CSMO). METHODS: Fifty-three patients (84 eyes) with diabetic CSMO were randomly assigned to MPDL (n = 44) or CGL (n = 40) according to the modified Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Treatments were performed after baseline and re-treatments were allowed at or after the 4 month visit if necessary. Parameters noted included the best corrected visual acuity (BCVA), colour fundus photographs, central retinal thickness using optical coherence tomography (OCT), vision contrast sensitivity with Pelli-Robson charts and presence of visible laser scars at baseline and at 4 and 12 months. The primary outcome was BCVA at 12 months. RESULTS: All patients completed 12 months of follow-up after treatment at baseline. There were no statistically significant differences in BCVA, contrast sensitivity and retinal thickness between the two laser modalities at 0, 4 and 12 months. We found that laser scarring was much more apparent with CGL than with the sub-threshold approach (MPDL). Laser scars were identified at the 12 month visits in 13.9% of the MPDL-treated eyes compared with 59.0% of the CGL-treated eyes (p<0.001). CONCLUSION: Sub-threshold micropulse diode laser photocoagulation is equally as effective as CGL treatment for CSMO. TRIAL REGISTRATION NUMBER: ISTRN 90646644.

Chorioretinal anastomosis and photodynamic therapy: a two-year follow-up study.

BACKGROUND: To evaluate the two-year efficacy of photodynamic therapy with Visudyne (PDT) in neovascular age-related macular degeneration (AMD) eyes with chorioretinal anastomosis (CRA). METHODS: A non-randomized, institutional, prospective study, of 28 consecutive eyes of 23 patients, with CRA, treated with PDT. Masked best corrected visual acuity (VA) and angiographic features at baseline and during the period of two years were evaluated. RESULTS: Twenty eight eyes completed one year and 19 eyes completed two years of follow-up. The number of treatments was 3 in the first year, and 0.8 in the second year. A VA loss < 3 lines occurred in 53% of the eyes, at two years. Treated eyes lost 0.5 lines in the first year and 2.4 lines in the second (p < 0.01). Recurrence with additional significant VA loss occurred in four eyes (21%) during the second year. Fourteen eyes (74%) showed no fluorescein leakage at two years. CONCLUSION: AMD eyes with chorioretinal anastomosis can benefit from PDT with Verteporfin at two years. However, during the second year significant additional VA loss occurs mainly due to recurrence. New modalities of treatment are necessary to achieve VA improvement in CRA eyes.

[The European Vision Institute. Opening up new frontiers?]. / Das "European Vision Institute". Aufbruch zu neuen Ufern?

The European Vision Institute EEIG (EVI) creates a new legal entity based on Community law to facilitate and encourage cross-border co-operation in vision research. Its major objectives are to conduct and support research, training, health information dissemination and other programmes with respect to blinding eye diseases, visual disorders, mechanisms of visual function, preservation of sight and the special health problems and requirements of the blind and visually disabled. EVI aims to foster centres in the EU in capacity building for innovative projects, to increase the flexibility, attractiveness and competitiveness of research careers, especially for young researchers. In addition, EVI will serve to co-ordinate activities with patient organisations and to build a pan-European platform for clinical trials.

Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin.

BACKGROUND: We evaluated, in a nonrandomised, institutional, prospective study, the efficacy of photodynamic therapy (PDT) with verteporfin in age-related macular degeneration (AMD) eyes with polypoidal choroidal vasculopathy (PCV) and subfoveal exudation. METHODS: A prospective clinical and angiographic study was done in 40 consecutive eyes with PCV treated with PDT using masked best-corrected visual acuity (VA) and fluorescein and indocyanine green angiographic features at baseline and over 2 years. RESULTS: Twenty-one eyes completed 1-year follow-up and showed, after a mean 2.9 PDT sessions, VA improvement in 12 eyes, no change in five eyes, and VA decrease in four eyes. Leakage was absent at the retinal and choroidal level in 14 eyes at 1 year. Recurrence occurred in one eye during the first year. Six eyes completed 2 years of follow-up and showed, after a mean 4 PDT sessions, VA improvement in five eyes and VA decrease in one eye. Leakage was absent at the retinal and choroidal level in five eyes. Recurrence occurred in four of these six eyes during the second year of follow-up. No serious adverse events were observed during the 2 years of follow-up. CONCLUSIONS: PDT with verteporfin was shown to be safe and effective for treating AMD eyes with PCV with subfoveal involvement. VA improvement and absence of leakage were achieved, respectively, in 57.1% and 66.6% of the eyes at 1 year. Recurrences were more frequent during the second year of follow-up.

Effects of neuropeptides on the sumatriptan-disturbed circulation in the optic nerve head of rabbits.

The purpose of this work was to study 'in vivo' the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E(max) (mean +/- SEM) 21.3 +/- 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E(max) 53.3+/-2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E(max) 41.1+/-0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E(max) 5.1+/-1.2 and 8.0+/-0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E(max) 43.2+/-2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.

Effects of ibopamine eye drops on intraocular pressure and aqueous humor flow in healthy volunteers and patients with open-angle glaucoma.

PURPOSE: On the basis of intraocular pressure measurements and fluorophotometry we assessed the effects of 2% ibopamine eye drops on aqueous humor production in normal and glaucomatous eyes. METHODS: Thirty subjects (15 healthy volunteers and 15 open-angle glaucoma patients with ocular hypertension) were included in a placebo-controlled study with random assignment of treatment from masked containers. All subjects underwent ophthalmologic examinations and intraocular pressure (IOP) measurements. Fluorophotometry was done in both eyes at baseline (without treatment) and during treatment. Each subject was treated with 1 drop of 2% ibopamine in one eye and 1 drop of placebo in the fellow eye 30 minutes before fluorophotometric scans and every hour after the first instillation (for a total of 4 times). Safety was evaluated by recording adverse events and ocular symptoms and signs. Aqueous humor flow data were analyzed using the paired t-test, comparing ibopamine and placebo-treated eyes. RESULTS: No changes in IOP were detected in normal eyes, whereas glaucomatous eyes showed a mean increase of 4 mmHg (95% CI 3.46-4.51) from baseline. The difference in IOP between healthy eyes and those with glaucoma was significant (p < 0.0001). In normal eyes and patients with glaucoma ibopamine led to a significant increase in aqueous humor flow compared with placebo-treated eyes (p < 0.01). The safety profile of ibopamine was very good. CONCLUSIONS: The results seem to confirm that ibopamine increases aqueous humor production in normal and glaucomatous eyes, raising IOP only in eyes with glaucoma.

Comparison of topical travoprost eye drops given once daily and timolol 0.5% given twice daily in patients with open-angle glaucoma or ocular hypertension.

PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.

One-year follow-up of blood-retinal barrier and retinal thickness alterations in patients with type 2 diabetes mellitus and mild nonproliferative retinopathy.

OBJECTIVE: To examine the 1-year alterations of the blood-retinal barrier and changes in retinal thickness occurring in the macular region in patients with type 2 diabetes mellitus and mild nonproliferative retinopathy. METHODS: We classified 12 eyes of 12 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy by 7-field stereoscopic fundus photography, levels 20 and 35 of Wisconsin grading, and examined them 3 times, at 6-month intervals, by fluorescein angiography, retinal leakage analyzer (RLA) (modified confocal scanning laser ophthalmoscope), and retinal thickness analyzer. The maps of retinal leakage and retinal thickness were aligned and integrated into one image. Data from the group of individuals with diabetes were compared with those from a healthy control population (n = 14; mean age, 48 years; age range, 42-55 years) to establish reference maps for the RLA and the retinal thickness analyzer. RESULTS: Areas of abnormally increased fluorescein sodium leakage and increased thickness were detected in all eyes examined at baseline. The sites of increased fluorescein leakage reached values as high as 483% above normal, but in 10 of the total 36 examinations performed, fluorescein leakage returned to normal levels. A statistically significant correlation was found between changes in hemoglobin A(1c) values and variations in percentage of abnormal fluorescein leakage between the 6- and 12-month examinations (P<.001). When comparing the RLA-leaking sites among the 3 examinations, a good correlation was seen among the location of these sites of maximum leakage, but there was a clear fluctuation in the percentage of increases. A correlation was noted between the location of the RLA-leaking sites and the location of areas of increased retinal thickness in subsequent examinations, either 6 or 12 months later. Microaneurysms showed relatively little leakage and leaked progressively less in successive examinations. CONCLUSIONS: The dominant alteration in the retina of patients with type 2 diabetes mellitus and mild nonproliferative retinopathy is the presence of RLA-leaking sites, indicating spotty retinal vascular damage characterized by alteration of the blood-retinal barrier. This damage appears to be reversible and directly associated with variations in glycemic metabolic control. Retinal edema appears to develop mainly as a result of retinal vascular leakage.

Alterations of the blood-retinal barrier and retinal thickness in preclinical retinopathy in subjects with type 2 diabetes.

OBJECTIVE: To identify alterations of the blood-retinal barrier by mapping retinal fluorescein leakage into the vitreous and changes in retinal thickness occurring in the macular region in preclinical diabetic retinopathy. METHODS: Ten eyes from 10 patients with type 2 diabetes and no lesions visible on fundus photography (level 10 of Wisconsin grading) were examined with the retinal leakage analyzer (RLA) (Confocal Scanning Laser Ophthalmoscope [modified]; Carl Zeiss Inc, Thornwood, NY) and the retinal thickness analyzer (RTA) (Talia Technology, Mevaseret Zion, Israel). The maps of retinal leakage and retinal thickness were aligned and integrated in the same image to correlate leakage with thickness. Data from the group of individuals with diabetes were compared with those of a healthy control population (N = 14; mean age, 48 years; range, 42-55 years) and used to establish reference maps for the RLA and RTA. RESULTS: Areas of abnormally increased fluorescein leakage were detected in 9 of 10 eyes examined. The increased leakage in 6 (67%) of 9 eyes reached values higher than 40% more than the mean +2 SD RLA control value. Areas of abnormally increased thickness were found in 7 of 10 eyes examined. For the most part, the increases in retinal thickness were not severe (ie, <15% increase in 5 eyes and an 18% increase in 1 eye). The eyes with the most extensive leakage (cases 1, 3, and 9) showed relatively good coincidence between the location of the areas of increased leakage and the location of the areas of increased thickness. In 4 eyes (cases 2, 5, 7, and 8), no such correlation was apparent. The 3 remaining eyes showed little coincidence between these locations. Characteristically, the latter 3 eyes had areas of abnormally increased thickness that were much larger than the areas of increased fluorescein leakage, which were relatively moderate or absent of any leakage. CONCLUSIONS: Localized sites of increased fluorescein leakage and zones of increased retinal thickness were found in most eyes in a series of 10 eyes in the preretinopathy stage from 10 patients with type 2 diabetes. Increases in retinal thickness may be observed that do not coincide with sites of retinal leakage. Two types of increased retinal thickness may, therefore, be present in the preretinopathy stage of diabetic retinopathy, one directly associated with an alteration of the blood-retinal barrier, and another occurring without apparent breakdown of blood-retinal barrier.

Diabetic retinopathy: surrogate outcomes for drug development for diabetic retinopathy.

Diabetic retinopathy remains the most frequent cause of new cases of blindness among adults aged 20-74 years. A number of large clinical trials have validated treatment methods now considered standard. However, the disease continues to progress in approximately 50% of the eyes treated by photocoagulation. Other forms of therapy targeted at the earliest stages of retinal disease are needed. The difficulties in defining and accepting surrogate outcomes appropriate to evaluate the earlier stages of retinopathy are discussed. Special attention is given to trial design and the most likely possibilities for surrogate outcomes: mean difference on the Early Treatment Diabetic Retinopathy Study retinopathy scale of at least 2 steps per eye, reduction in macular thickening and reduction in fluorescein leakage.

Effect of cyclosporin-A on the blood--retinal barrier permeability in streptozotocin-induced diabetes.

BACKGROUND: Our previous results showed that in retinas from streptozotocin (STZ)-induced diabetic rats there is an increased level of interleukin-1beta (IL-1beta). This cytokine may be involved in the expression of the inducible isoform of the nitric oxide synthase (iNOS), with consequent synthesis of large amounts of NO and blood-retinal barrier (BRB) breakdown. AIMS: The aim of this work was to examine whether the administration of cyclosporin-A (Cs-A) to STZ-induced diabetic rats inhibits the synthesis of IL-1beta and the expression of the inducible proteins, iNOS and cyclo-oxygenase-2 (COX-2) in retinal cells, and whether the activity of these proteins contribute to BRB breakdown. METHODS: The level of IL-1beta was evaluated by ELISA and the NO production by L-[3H]-citrulline formation. Expression of iNOS and COX-2 proteins was determined by two methods, western blot and immunohistochemistry. The permeability of the BRB was assessed by quantification of the vitreous protein. RESULTS AND DISCUSSION: Our results indicated that the levels of IL-1beta and NO in retinas from Cs-A-treated diabetic rats are significantly reduced, as compared to that in non-treated diabetic rats. The treatment of diabetic rats with Cs-A also significantly inhibited the expression of the inducible proteins, iNOS and COX-2. The evaluation of the vitreous protein content revealed that Cs-A also reduces the BRB permeability. Taken together, these results suggest that the increased production of the inflammatory mediators, IL-1beta and NO, in diabetes may affect the BRB permeability and therefore contribute to the development of diabetic retinopathy.

Nitric oxide synthase activity in retinas from non-insulin-dependent diabetic Goto-Kakizaki rats: correlation with blood-retinal barrier permeability.

The aim of this work was to examine whether the non-insulin-dependent diabetic Goto-Kakizaki (GK) rats develop retinal changes with similar characteristics to those observed in insulin-dependent diabetic rats in what concerns blood-retinal barrier (BRB) permeability, nitric oxide (NO) production, and retinal IL-1beta level. BRB permeability was evaluated by vitreous fluorophotometry. NO synthase (NOS) activity was assessed by the production of l-[(3)H]-citrulline and retinal IL-1beta level was determined by ELISA. The expression of the inducible isoform of NOS (iNOS) protein was evaluated by Western blot analysis and immunohistochemistry. The in vivo studies indicated that in GK rats the BRB permeability to fluorescein was increased (787.81 +/- 68 min(-1)) in comparison to that in normal Wistar rats (646.6 +/- 55 min(-1)). The ex vivo studies showed that in retinas from GK rats the NOS activity was higher (207 +/- 28.9 pmol l-[(3)H]-citrulline/mg protein/30 min) than that in normal Wistar rats (125 +/- 32.3 pmol l-[(3)H]-citrulline/mg protein/30 min). These results were correlated with an increase in the protein level of iNOS in the retinas of GK rats, which was confirmed not only by the study of the iNOS protein expression but also by the use of NOS activity inhibitors. Indeed, the data about the effect of specific inhibitors on the NOS activity revealed that in retinas from GK rats the most effective inhibitor was aminoguanidine, which predominantly inhibits the iNOS isoform whereas in retinas from normal Wistar rats it was N(G) nitro l-arginine that predominantly inhibits the constitutive isoforms of NOS. In summary, in retinas from GK rats there is an increased production of NO which may contribute to the BRB breakdown.

Mapping retinal fluorescein leakage with confocal scanning laser fluorometry of the human vitreous.

OBJECTIVE: To demonstrate an objective, quantitative, and sensitive method of mapping retinal fluorescein leakage into the vitreous while simultaneously imaging the retina. METHODS: A prototype Zeiss confocal scanning laser ophthalmoscope was modified to obtain fluorometric measurements from 18 optical planes across the retina and cortical vitreous, separated from each other by 150 microm, and parallel to the retinal surface. After intravenous administration of fluorescein, an axial graphic of equivalent fluorescein concentration in the vitreous may be obtained from any region of interest. After correcting for fluorescence levels in the retina and choroid and plasma levels of free fluorescein, permeability values of the blood-retinal barrier to fluorescein were obtained from 1512 regions measuring 75 x 75 microm, from a total 3150 x 2700-microm area of the fundus, generating a detailed map of retinal fluorescein leakage. The method was assessed in vitro and in 7 healthy subjects who underwent scans during separate visits. Depth resolution and influence of chorioretinal fluorescence were further tested in 2 patients with multiple drusen and in 2 eyes after vitrectomy. Fourteen eyes from 7 patients with diabetes and nonproliferative retinopathy were also examined. Lateral resolution was tested in 3 diabetic eyes that underwent focal photocoagulation. Four eyes from 2 patients with diabetes and minimal retinopathy were examined at 3-month intervals. All eyes examined had less than 2 diopters of astigmatism. RESULTS: Characteristics of the modified confocal scanning laser fluorometer included a lower limit of detection equal to 0.40 Eq ng/mL and depth precision of +/-15 microm. Values for the blood-retinal barrier permeability index in healthy subjects, measured 30 minutes after a single intravenous pulse of fluorescein (14 mg/kg), ranged from 1.3 +/- 0.4 x 10(-6) cm/s over the foveal avascular zone to 2.2 +/- 0.6 x 10(-6) cm/s over vessels in the retina. Diabetic eyes with retinopathy showed higher values, ranging from 1.4 to 15.0 x 10(-6) cm/s. Vitrectomized eyes and eyes with multiple drusen showed the validity of the correction algorithm demonstrating that measurements of fluorescence in the vitreous are not influenced by the chorioretinal fluorescence level. Argon laser photocoagulation burns placed in the diabetic retina demonstrated a lateral resolution on the order of 75 to 100 microm. Intravisit and intervisit reproducibility was +/-10.2% and +/-13%, respectively. CONCLUSIONS: This new method measures localized alterations of the blood-retinal barrier and allows for direct correlation with retinal anatomy. Its most interesting feature is the ability to map retinal fluorescein leakage while simultaneously imaging the retina. This capability is expected to improve our understanding and management of retinal disease.

Novel imaging techniques for diabetic macular edema.

Retinal edema should be defined as any increase of water of the retinal tissue resulting in an increase in its volume. It may be of cytotoxic or vasogenic origin. Development of vasogenic macular edema is dependent on a series of factors such as blood pressure, blood-retinal barrier permeability, retinal cell damage, retinal tissue osmotic pressure and retinal tissue compliance. Objective measurements of retinal thickness are now possible using the Retinal Thickness Analyser. Localised measurements of blood-retinal barrier permeability may also be obtained using the Retinal Leakage Analyser, a modified confocal scanning laser fluorometer, while obtaining simultaneously angiographic images of the choroid and retina. These new imaging techniques show that cytotoxic and vasogenic retinal edema may occur independently in the early stages of diabetic retinopathy. These findings offer new perspectives for designing novel therapeutic strategies.