[Photo-based examination for diabetic eye pathologies in a German ophthalmological practice without personal doctor-patient contact]. / Fotobasierte Untersuchung auf diabetische Augenveränderungen in einer deutschen Augenarztpraxis ohne direkten Arzt-Patienten-Kontakt.

BACKGROUND: An increasing number of patients suffering from diabetes require regular ophthalmological check-ups to diagnose and/or treat potential diabetic retinal disease. Some countries have already implemented systematic fundus assessments including artificial intelligence-based programs in order to detect sight-threatening retinopathy. The aim of this study was to improve the detection of diabetic fundus changes in Germany without examination by a doctor and to create an easy access to ophthalmological examinations. MATERIAL AND METHODS: In this prospective monocentric study 93 patients in need for a routine check-up for diabetic retinopathy were included. The study participants took up an offer of an examination (visual examination, non-mydriatic camera-based fundus examination) without doctor-patient contact. Patient satisfaction with the organization and examinations was assessed using a questionnaire. RESULTS: The mean age was 53.5 years (SD 13.6 years, 49.5% female) and 17 eyes (18.3%) showed a diabetic retinopathy which was detected using a camera-based examination. Within the small sample, no patient had to repeat the examination due to poor image quality. All categories of the questionnaire showed a good to very good satisfaction, indicating a high acceptance of the other examination form that took place at the ophthalmologist's premises. CONCLUSION: In our study in an ophthalmological practice a high level of acceptance among the patients interested in the screening for diabetic retinopathy without any direct patient-doctor contact was achieved. Our study shows a very good acceptance and feasibility. Future use of artificial intelligence in clinical practice may help to be able to screen many more patients as in this study imaging quality was very good.

Detection of SARS-CoV-2-RNA in post-mortem samples of human eyes.

PURPOSE: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. METHODS: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. RESULTS: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. CONCLUSION: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.

[The Eye in Internal Medicine: Diabetic retinopathy]. / Das Auge in der Inneren Medizin: Die diabetische Retinopathie.

Diabetic retinopathy has seen tremendous progress in diagnostic tools and treatment in recent 15 years. Sight threatening stages like proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) can be treated much more effectively now. The recognition of vascular endothelial growth factor (VEGF) as a driver of proliferation and macular edema has led to the development of VEGF inhibiting drugs such as antibodies (Bevacizumab), fragments of an antibody (Ranibizumab), or a so called VEGF trap (Aflibercept). Laser treatment is no longer a gold standard. Today laser therapy is part of a combined treatment strategy. DME can be monitored quantitatively by ocular coherence tomography (OCT) measurements. For non-responders to VEGF inhibiting drugs, we have secondline corticosteroidal implants. However, screening examinations and early diagnosis of DME and PDR remain crucial. The same accounts for the collaboration of opthalmologists, general practioners, and diabetologists. Good control of diabetes and blood pressure is still important.

[Cost Comparison of Licensed Intravitreal Therapies for Insufficiently Anti-VEGF Responding Fovea Involving Diabetic Macular Edema in Germany]. / Kostenvergleich zugelassener intravitrealer Therapien bei nicht ausreichend auf primäre Therapie ansprechendem diabetischem Makulaödem mit fovealer Beteiligung in Deutschland.

BACKGROUND: In the treatment of center-involving diabetic macular edema, despite initial therapy with an anti-VEGF compound, an insufficient response may occur. Further therapy options include a switch of anti-VEGF products or to corticosteroid implants, such as Fluocinolone acetonide or Dexamethasone. OBJECTIVES: Firstly, to investigate systematically which evidence-based study data are available describing the efficacy of in-label treatments after primary anti-VEGF treatment, secondly, to investigate which costs go along for the healthcare provider. METHODS: A systematic literature review (SLR) for randomized controlled trials (RCT) was performed in Medline and Embase. A short-term cost-cost model was built in MS Excel with a 3 year time horizon to compare in-label intravitreal options Ranibizumab (Lucentis®), Aflibercept (Eylea®), Fluocinolone acetonide implant (Iluvien®), and Dexamethasone implant (Ozurdex®). Cost components comprised of drug and injection costs, optical coherence tomography (OCT) procedures, and adverse events such as endophthalmitis, IOP-lowering drugs and surgery and cataract surgery. RESULTS: A total of 42 publications of 20 RCTs were identified. No study had a clearly defined population after first line anti-VEGF treatment, thus no direct efficacy comparison was possible. In the short-term cost-cost model total costs were 17,542 € for Ranibizumab, 15,896 € for Aflibercept, 10,826 € for Fluocinolone acetonide implant and 12,365 € for Dexamethasone implant. For all treatment regimens, drug costs were the predominant cost component, followed by injection costs (with variations dependent on the specific drug) and OCT costs. In the uni- and multivariate sensitivity analyses, the results obtained were robust to changes of model inputs. CONCLUSIONS: In summary, the short-term cost-cost comparison demonstrates that steroid implants can provide significant cost savings versus in-label anti-VEGF treatment for center-involving diabetic macular edema. Single application of the long-lasting Fluocinolone acetonide implant is the most cost-efficient in-label treatment option.

Evaluation of a computed-tomography-based assessment scheme in treatment decision-making for isolated orbital floor fractures.

INTRODUCTION: Treatment decisions for fractures of the orbital floor are based on clinical appearance, ophthalmological examination, and computed tomography (CT) scans. In extensive fractures, decisions are easily made between conservative and surgical treatment. However, objective parameters are rare in inconclusive cases. MATERIALS AND METHODS: Our retrospective study included 106 patients with unilateral isolated orbital floor fractures. Correlations between preoperative ophthalmological examinations and specific CT parameters were performed. RESULTS: The defect size of the fracture appeared to be significantly associated with the presence of diplopia. CT-morphological parameters and preoperative ophthalmological results showed statistical significance for diplopia and incarceration of inferior rectus muscle (IRM), diplopia and displacement of IRM, decreased mobility and incarceration of IRM, and decreased mobility and displacement of IRM. DISCUSSION: Our clinical assessment scheme for CT scans of orbital floor fractures is aimed at facilitating treatment decision making using four CT-based variables. As critical size defects of the orbital floor of ≥2 cm2 are likely to cause clinically significant posterior displacement of the globe, resulting in enophthalmos, the proposed parameters offer a readily accessible and easy to evaluate scheme that helps to identify patients in need of surgical intervention.

A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS).

PURPOSE: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. METHODS: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. RESULTS: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3-5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) µm, and the mean change in CRT was -115.2 µm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). CONCLUSION: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring.

Structure-function relationship comparison between retinal nerve fibre layer and Bruch's membrane opening-minimum rim width in glaucoma.

AIM: To evaluate and compare structural optical coherence tomography (OCT)-based parameters, such as Bruch's membrane opening-minimum rim width (BMO-MRW), and retinal nerve fiber layer (RNFL) thickness in glaucoma patients with visual field (VF) defects, and to correlate both to mean deviation (MD) values of obtained standard achromatic perimetry (SAP) examinations. METHODS: Patients with glaucoma and glaucomatous VF defects were enrolled in this prospective study and compared to age-matched healthy individuals. All study participants underwent a full ophthalmic examination and VF testing with SAP. Peripapillary RNFL thickness and BMO-MRW were acquired with SD-OCT. Correlation analyses between obtained global functional and global as well as sectorial structural parameters were calculated. RESULTS: A consecutive series of 30 glaucomatous right eyes of 30 patients were included and compared to 36 healthy right eyes of 36 individuals in the control group. Global MD of values correlated significantly with global RNFL (Pearson corr. coeff: 0.632, P=0.001) and global BMO-MRW (Pearson corr. coeff: 0.746, P<0.001) values in the glaucoma group. Global MD and sectorial RNFL or BMO-MRW values correlated less significantly. In the control group, MD values did not correlate with RNFL or BMO-MRW measurements. A subgroup analysis of myopic patients (>4 diopters) within the glaucoma group (n=6) revealed a tendency for higher correlations between MD and BMO-MRW than MD and RNFL measurements. CONCLUSION: In a clinical setting, RNFL thickness and BMO-MRW correlate similarly with global VF sensitivity in glaucoma patients with BMO-MRW showing higher correlations in myopic glaucoma patients.

Long-term results and recurrence rates after spironolactone treatment in non-resolving central serous chorio-retinopathy (CSCR).

PURPOSE: To evaluate the long-term results of spironolactone in non-resolving central serous chorio-retinopathy (CSCR) and recurrence rates of CSCR. METHODS: Interventional uncontrolled open-label prospective clinical trial of patients with non-resolving CSCR who were treated with spironolactone 50 mg daily (Spironolacton AL® 50 mg, ALIUD PHARMA) for up to 16 weeks. Follow-up visits were performed at 3, 6, 9, and 12 months. Retreatment criteria for recurrence were: gain in sub-retinal fluid (SRF) of more than 25 % plus/or increase of central retinal thickness (CRT) of more than 50 µm plus visual symptoms compared to last visit. MAIN OUTCOME MEASURES: 12-month efficacy of upload treatment with spironolactone. Secondary outcome measure was the recurrence rate at 6, 9, and 12 months. RESULTS: Of the 21 study eyes treated, 71 % (n = 15) showed significant improvement or complete regression on OCT examination over 12 months. Nineteen percent of the patients (n = 4) showed a stable course from visit 1 to visit 12. The overall reduction of sub-retinal fluid from visit 1 (156 µm ± 131 SD) to visit 12 (53 µm ± 93 SD) was statistically significant (p = 0.003). The change of mean visual acuity (log MAR) from 0.25 (± 0.17 SD) at baseline to 0.17 (± 0.18 SD) at visit 12 was statistically significant, with p = 0.044. CONCLUSION: Our results confirm a positive effect of spironolactone in non-resolving CSCR in 71 % of cases. Evaluation of recurrence rates and retreatments showed good results in patients who responded to spironolactone primarily. A prospective randomized trial may provide better data about this non-invasive treatment.

Diabetic retinopathy - ocular complications of diabetes mellitus.

In industrialized nations diabetic retinopathy is the most frequent microvascular complication of diabetes mellitus and the most common cause of blindness in the working-age population. In the next 15 years, the number of patients suffering from diabetes mellitus is expected to increase significantly. By the year 2030, about 440 million people in the age-group 20-79 years are estimated to be suffering from diabetes mellitus worldwide (prevalence 7.7%), while in 2010 there were 285 million people with diabetes mellitus (prevalence 6.4%). This accounts for an increase in patients with diabetes in industrialized nations by 20% and in developing countries by 69% until the year 2030. Due to the expected rise in diabetic patients, the need for ophthalmic care of patients (i.e., exams and treatments) will also increase and represents a challenge for eye-care providers. Development of optimized screening programs, which respect available resources of the ophthalmic infrastructure, will become even more important. Main reasons for loss of vision in patients with diabetes mellitus are diabetic macular edema and proliferative diabetic retinopathy. Incidence or progression of these potentially blinding complications can be greatly reduced by adequate control of blood glucose and blood pressure levels. Additionally, regular ophthalmic exams are mandatory for detecting ocular complications and initiating treatments such as laser photocoagulation in case of clinical significant diabetic macular edema or early proliferative diabetic retinopathy. In this way, the risk of blindness can considerably be reduced. In advanced stages of diabetic retinopathy, pars-plana vitrectomy is performed to treat vitreous hemorrhage and tractional retinal detachment. In recent years, the advent of intravitreal medication has improved therapeutic options for patients with advanced diabetic macular edema.

Comparative evaluation of combined navigated laser photocoagulation and intravitreal ranibizumab in the treatment of diabetic macular edema.

OBJECTIVE: To evaluate if a standardized combination therapy regimen, utilizing 3 monthly ranibizumab injections followed by navigated laser photocoagulation, reduces the number of total ranibizumab injections required for treatment of diabetic macular edema (DME). RESEARCH DESIGN AND METHODS: A 12-month, prospective comparison of 66 patients with center-involving DME: 34 patients with combination therapy were compared to 32 patients treated with ranibizumab monotherapy. All patients initially received 3 monthly ranibizumab injections (loading phase) and additional injections pro re nata (PRN). Combination therapy patients additionally received navigated laser photocoagulation after the loading phase. Main outcome measures were mean number of injections after the loading phase and change in BCVA from baseline to month 12. RESULTS: Navigated laser combination therapy and ranibizumab monotherapy similarly improved mean BCVA letter score (+8.41 vs. +6.31 letters, p = 0.258). In the combination group significantly less injections were required after the 3 injection loading phase (0.88 ± 1.23 vs. 3.88 ± 2.32, p< = 0.001). By month 12, 84% of patients in the monotherapy group had required additional ranibizumab injections as compared to 35% in the combination group (p< = 0.001). CONCLUSIONS: Navigated laser combination therapy demonstrated significant visual gains in most patients. Retreatment rate and number of injections were significantly lower compared to ranibizumab monotherapy and compared to the results of conventional laser combination therapy previously reported in pivotal anti-VEGF studies.

Assessment of ß-zone peripapillary atrophy by optical coherence tomography and scanning laser ophthalmoscopy imaging in glaucoma patients.

PURPOSE: To assess ß-zone peripapillary atrophy (ß-PPA) using spectral domain optical coherence tomography (SD-OCT), scanning laser ophthalmoscopy (SLO), and fundus auto-fluorescence (FAF) imaging in patients with primary open-angle glaucoma with advanced glaucomatous visual field defects. METHODS: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma were included in this study. All study participants underwent a full ophthalmic examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic nerve head and the peripapillary region. RESULTS: Eighty-four glaucomatous eyes were included in our prospective study. Correlation analyses for horizontally and vertically obtained ß-PPA for all three imaging modalities (color SLO, FAF, and SD-OCT) revealed highest correlations between FAF and color SLO (Pearson correlation coefficient: 0.904 [P<0.001] for horizontal ß-PPA and 0.786 [P<0.001] for vertical ß-PPA). Bland-Altman plotting revealed highest agreements between color SLO and FAF, with -2.1 pixels ±1.96 standard deviation (SD) for horizontal ß-PPA, SD: 10.5 pixels and 2.4 pixels ±1.96 SD for vertical ß-PPA. CONCLUSION: ß-PPA can be assessed using en-face SLO and cross-sectional SD-OCT imaging. Correlation analyses revealed highest correlations between color SLO and FAF imaging, while correlations between SLO and SD-OCT were weak. A more precise structural definition of ß-PPA is needed.

Visual acuity and central retinal thickness: fulfilment of retreatment criteria for recurrent neovascular AMD in routine clinical care.

BACKGROUND: To evaluate the fulfillment of retreatment criteria in recurrent neovascular age-related macular degeneration (nAMD) for a pro-re-nata treatment regime with ranibizumab in routine clinical care. METHODS: Data from patients with treatment-naive nAMD were analysed retrospectively. As an 'upload', all patients had received three-monthly intravitreal ranibizumab injections in a university eye hospital and were then seen by ophthalmologists in private practice who referred them back in case of recurrence. Recurrence was defined as a decrease of visual acuity (VA) of one line or more (functional retreatment criteria), a central retinal thickness (CRT) increase of at least 100 µm upon Optical Coherence Tomography (OCT) examination (morphological retreatment criteria) or a new macular haemorrhage (clinical retreatment criteria). RESULTS: We included 92 patients (36 men and 56 women). The mean VA before retreatment of a recurrence was -0.63 ± 0.33 logMAR and improved significantly (p<0.001) by 0.10 ± 0.16 logMAR to -0.53 ± 0.28 logMAR thereafter. Mean CRT before retreatment was 278.07 ± 87.56 µm and decreased significantly (p<0.001) by 71.22 ± 106.93 to 206.85 ± 60.30 µm. Evaluation of the fulfillment of retreatment criteria revealed functional retreatment criteria in 82.6% of patients. However, upon re-evaluation of VA using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in the treatment centre, mean decrease of VA was 10 letters as compared with the end of upload therapy. All patients presented an increased CRT when treated for recurrence of nAMD (mean increase 69.47 µm), but the morphological retreatment criteria (CRT increase of 100 µm or more) were fulfilled in only 44.4% of patients upon Spectral Domain OCT (SD-OCT) evaluation in the treatment centre. CONCLUSIONS: In a routine clinical care, evaluation of VA using ETDRS charts seems to be more sensitive than Snellen VA testing. Quantitative OCT-based retreatment criteria (eg, increase of CRT of 100 µm or more) appear to be not sensitive enough in a clinical setting with referring ophthalmologists.

Scanning laser 'en face' retinal imaging of epiretinal membranes.

PURPOSE: Comparison of scanning laser ophthalmoscopy (SLO) based 'en face' imaging techniques of patients with epiretinal membranes (ERM) and evaluation of the accuracy of preoperative diagnostic imaging. METHODS: A consecutive, prospective series of 53 study eyes of 46 patients with clinically diagnosed and in optical coherence tomography (OCT) confirmed symptomatic ERMs were included in this study. Spectral domain (SD-) OCT volume scans (20° × 20° with 49 horizontal sections, ART 15) including SLO en face and fundus autofluorescence (FAF) images of the macula were obtained with HRA2 (Heidelberg Retina Angiograph-Optical Coherence Tomography, Heidelberg Engineering, Heidelberg, Germany). In addition, wide-field SLO color and FAF images (Optomap 200Tx, Optos PLC, Dunfermline, UK) were performed also covering the macular area. En face images of both devices were graded for each included study eye based on SD-OCT cross sectional scans. RESULTS: Grading of SD-OCT (HRA2) based SLO en face green-blue enhanced multi-color, green reflectance, blue reflectance and standard multi-color visualization revealed a better detectability of ERM than SD-OCT-based en face infrared or FAF images or wide-field SLO (Optomap) based pseudo-color, red laser separation, green laser separation, or FAF images. Both FAF visualizations, HRA2 and Optomap based, achieved low mean scores. SD-OCT based en face thickness map visualization revealed good visualization but poor demarcation of epiretinal membranes. CONCLUSIONS: In summary, en face regular or enhanced multicolor SLO images acquired with HRA2 allow a better visualization of epiretinal membranes for preoperative evaluation compared to SD-OCT based en face thickness map or pseudo-color images acquired with Optomap while infrared or FAF images are least suitable to depict epiretinal membranes.

Central serous chorioretinopathy.

The pathogenesis of central serous chorioretinopathy (CSC) is still not fully understood. The involvement of corticosteroids is undisputed, although their exact role has not been clarified; other parts of the underlying mechanism of CSC have been mainly elucidated by imaging techniques such as fluorescein and indocyanine green angiography. Even though most cases of CSC are self-limiting, severe as well as recurrent courses exist, and for these patients only a limited number of treatment options are available: laser photocoagulation, with a risk of scotoma and choroidal neovascularization, and photodynamic therapy. In this review article, we give an overview of its epidemiology, the current understanding of its pathogenesis as well as systemic and ocular risk factors. We illuminate modern diagnostic tools as well as current treatment options in the context of CSC, particularly in the light of a better understanding of corticosteroids and their receptors involved in its pathogenesis.

Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment.

PURPOSE: To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy. METHODS: Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT. RESULTS: At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm). CONCLUSION: The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased.

Nonmydriatic ultra-wide-field scanning laser ophthalmoscopy (Optomap) versus two-field fundus photography in diabetic retinopathy.

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.

Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. METHODS: Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. RESULTS: The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. CONCLUSION: Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.