Clinical Utilisation of Wide-Field Optical Coherence Tomography and Angiography: A Narrative Review.

Many important abnormalities of the vitreous, retina and choroid are predominantly located in the peripheral retina. In some retinal diseases with both central and peripheral manifestations, pathological structural or vascular changes can be apparent in the periphery before they are detectable in the central retina. Conventional optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) imaging only cover the most posterior 30° of the retina. Wide-field OCT (WF-OCT), though offering detailed cross-sectional imaging of the peripheral retina, is not yet systematically used in clinical practice. This narrative review provides a presentation of the utilisation of WF-OCT and WF-OCT-A in the diagnosis and monitoring of a variety of ophthalmological diseases and discusses the advantages and limitations of the technology. With the rapidly developing technology, multiple WF-OCT and WF-OCT-A devices are now commercially available and enable the clinician to obtain scans within a field of view up to 200°. As detailed in this review, several studies have shown promising results in the application of WF-OCT and WF-OCT-A in diseases of the retina, choroid and vitreous, such as retinal vein occlusion, diabetic retinopathy, ocular oncology, paediatric ophthalmology, uveitis and lesions of the vitreo-retinal interface. In conclusion, WF-OCT and WF-OCT-A can reliably produce high-quality, non-invasive images of the vitreous, retinal, and choroidal structures and vascularity covering the posterior pole as well as the mid and far periphery. These methods can be a valuable part of a multimodal imaging approach in the management of a variety of ocular conditions. Future studies are warranted to investigate the patient outcome benefits of implementation of WF-OCT and WF-OCT-A imaging in a real-life clinical setting.

Present and future screening programs for diabetic retinopathy: a narrative review.

Diabetes is a prevalent global concern, with an estimated 12% of the global adult population affected by 2045. Diabetic retinopathy (DR), a sight-threatening complication, has spurred diverse screening approaches worldwide due to advances in DR knowledge, rapid technological developments in retinal imaging and variations in healthcare resources.Many high income countries have fully implemented or are on the verge of completing a national Diabetic Eye Screening Programme (DESP). Although there have been some improvements in DR screening in Africa, Asia, and American countries further progress is needed. In low-income countries, only one out of 29, partially implemented a DESP, while 21 out of 50 lower-middle-income countries have started the DR policy cycle. Among upper-middle-income countries, a third of 59 nations have advanced in DR agenda-setting, with five having a comprehensive national DESP and 11 in the early stages of implementation.Many nations use 2-4 fields fundus images, proven effective with 80-98% sensitivity and 86-100% specificity compared to the traditional seven-field evaluation for DR. A cell phone based screening with a hand held retinal camera presents a potential low-cost alternative as imaging device. While this method in low-resource settings may not entirely match the sensitivity and specificity of seven-field stereoscopic photography, positive outcomes are observed.Individualized DR screening intervals are the standard in many high-resource nations. In countries that lacks a national DESP and resources, screening are more sporadic, i.e. screening intervals are not evidence-based and often less frequently, which can lead to late recognition of treatment required DR.The rising global prevalence of DR poses an economic challenge to nationwide screening programs AI-algorithms have showed high sensitivity and specificity for detection of DR and could provide a promising solution for the future screening burden.In summary, this narrative review enlightens on the epidemiology of DR and the necessity for effective DR screening programs. Worldwide evolution in existing approaches for DR screening has showed promising results but has also revealed limitations. Technological advancements, such as handheld imaging devices, tele ophthalmology and artificial intelligence enhance cost-effectiveness, but also the accessibility of DR screening in countries with low resources or where distance to or a shortage of ophthalmologists exists.

Lack of stereopsis does not reduce surgical performance but prolongs the learning curve of vitreoretinal surgery.

PURPOSE: To investigate whether individuals with long-term reduced stereopsis were able to obtain the same level of surgical skills in simulated vitreoretinal surgery on the Eyesi Surgical Simulator as individuals with normal stereopsis. METHODS: Twenty-four medical students were recruited and divided into two groups according to their degree of stereopsis: Group 1 (n = 12) included subjects with normal stereopsis (60 arcsec or lower) and Group 2 (n = 12) included subjects with reduced stereopsis (120 arcsec or higher). Stereopsis was tested using the TNO test (Lameris Ootech BV, Nieuwegein, the Netherlands). The participants were trained in virtual reality-simulated vitreoretinal surgery and continuously measured using a test with solid validity evidence and a pre-defined pass-fail score. All data were analysed using the Wilcoxon rank sum test. RESULTS: We observed no differences in overall performance scores for any of the four modules. The participants with reduced stereopsis used 5.8 more attempts in bimanual training (p = 0.04), 8.8 more attempts in removal of posterior hyaloid (p = 0.04), 9.1 more attempts in navigation training (p = 0.20) and 0.3 fewer attempts in removal of internal limiting membrane (p = 0.69). CONCLUSION: The final performance scores on the Eyesi Surgical Simulator were independent of the degree of stereopsis. However, the number of attempts to achieve the pre-defined pass-fail score increased significantly with reduced stereopsis in two of four modules. These results indicate that a high degree of stereopsis is not necessary to become proficient in microsurgery but may prolong the learning curve.

Clinical Trials and Future Outlooks of the Port Delivery System with Ranibizumab: A Narrative Review.

The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100 mg/ml was 15.8 months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase 3 ARCHWAY trial reported that PDS with RBZ (100 mg/ml) refilled every 24 weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5 mg) in patients with nAMD over 9 months and 2 years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.

Retinal vascular structure independently predicts the initial treatment response in neovascular age-related macular degeneration.

PURPOSE: Prediction of the early treatment response is important in neovascular age-related macular degeneration (nAMD). Hence, we aimed to test if non-invasive measurements of the retinal vascular structure were able to predict a successful outcome of initial intravitreal treatment. METHODS: In 58 eyes of 58 patients with treatment-naïve nAMD, advanced markers of retinal vascular structure were measured by Singapore I Vessel Assessment prior to initial intravitreal treatment with three monthly injections of aflibercept with subsequently categorization of patients as full treatment responders (FTR) or non/partial treatment responders (N/PR), with the former defined as loosing fewer than five Early Treatment Diabetic Retinopathy Study letters and having no residual intra- or subretinal fluid or macular haemorrhage. RESULTS: Of 54 eyes attending follow-up, 44.4% were categorized as FTR. Patients with FTR were older (81.5 vs. 77 years, p = 0.04), and prior to treatment those eyes had a lower retinal arteriolar fractal dimension (Fd) (1.21 vs. 1.24 units, p = 0.02) and venular length-diameter ratio (LDR) (7.3 vs. 15.9 units, p = 0.006), but did not differ with respect to other retinal vascular parameters. In multiple logistic regression models, a lower chance of FTR was independently predicted by a higher retinal venular LDR (odds ratio [OR] 0.91, 95% CI 0.82-0.99, p = 0.03, for each 1 unit increment) and marginally by a higher retinal arteriolar Fd (OR 0.83, 95% CI 0.68-1.00, p = 0.05, for each 0.01 unit increment). CONCLUSION: Retinal venular LDR independently predicted the initial treatment response in nAMD. If confirmed by long-term, prospective studies, this might help to guide treatment.

Predictive value of retinal oximetry, optical coherence tomography angiography and microperimetry in patients with treatment-naïve branch retinal vein occlusion.

Vascular endothelial growth factor inhibitors have substantially improved the visual outcomes in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), but treatment outcomes are highly variable and early prediction of expected clinical outcome would be important for individualized treatment.As non-invasive metabolic, structural and functional retinal markers might act as early predictors of clinical outcomes, we performed a 12-month, prospective study aimed to evaluate if baseline retinal oximetry, optical coherence tomography angiography (OCT-A) or microperimetry were able to predict need of treatment, structural or functional outcome in patients with ME caused by treatment-näive BRVO.We evaluated 41 eyes of 41 patients with a mean age of 69.6 years and 56% females. We found a strong tendency towards a higher retinal arteriolar oxygen saturation in patients without a need of additional aflibercept treatment after the loading phase (99.8% vs. 92.3%, adjusted odds ratio 0.80 (95% confidence interval 0.64-1.00), adjusted p = 0.058), but otherwise, retinal oximetry, OCT-A or microperimetry were not able to predict need of treatment, structural nor functional outcomes. (Trial registration: clinicaltrials.gov, S-20,170,084. Registered 24 August 2014, https://clinicaltrials.gov/ct2/show/NCT03651011 ).

Investigation of the correlation between diabetic retinopathy and prevalent and incident migraine in a national cohort study.

Migraine is a disease characterized by cerebral vasodilation. While diabetes has previously been associated with a lower risk of migraine, it is not known if diabetic retinopathy (DR), a retinal peripheral vascular occlusive disease, is a potential biomarker of protection against migraine. Therefore, we aimed to examine diabetic retinopathy as a marker of prevalent and 5-year incident migraine. In a national cohort, we compared patients with diabetes attending DR screening from The Danish National Registry of Diabetic Retinopathy (cases, n = 205,970) to an age- and gender-matched group of patients without diabetes (controls, n = 1,003,170). In the cross-sectional study, a multivariable model demonstrated a lower prevalence of migraine among cases compared with controls (OR 0.83, 95% CI 0.81-0.85), with a lower risk in cases with DR than in those without (OR 0.69, 95% CI 0.65-0.72). In the prospective study, a lower risk of incident migraine was found in a multivariable model in cases (HR 0.76, 95% CI 0.70-0.82), but this did not depend upon the presence of DR. To conclude, in a national study of more than 1.2 million people, patients screened for DR had a lower risk of present migraine, but DR was not a protective marker of incident migraine.

Navigated laser and aflibercept versus aflibercept monotherapy in treatment-naïve branch retinal vein occlusion: A 12-month randomized trial.

PURPOSE: Angiostatic agents have proven effective in the treatment of macular oedema in patients with branch retinal vein occlusion (BRVO). However, treatment is inconvenient and expensive, and novel treatment regimens are warranted. We aimed to evaluate if combination treatment of navigated central retinal laser and aflibercept lowered the treatment burden in these patients. METHODS: Treatment-naïve patients with BRVO and macular oedema were included at two centres and randomized 1:1 to three monthly injections of 2.0 mg aflibercept with (Group A) or without (Group B) navigated central laser, followed by aflibercept as needed from month 4 through 12. Re-treatment need was evaluated, and secondary endpoints included functional and anatomical outcomes and safety evaluated by retinal microperimetry. RESULTS: We evaluated 41 eyes of 41 patients with a mean age of 69.6 years. Baseline median best-corrected visual acuity (BCVA) was 70.0 letters, and median central retinal thickness (CRT) was 502 µm with no difference between Groups A (n = 21) and B (n = 20). Percentage of patients needing re-treatment after month three was 71% and 80% (p = 0.72). At month 12, groups did not differ in number of injections after loading (1 versus 2, p = 0.43), change in BCVA (+12.8 versus +15.1 letters, p = 0.48), CRT (-195 versus -181 µm, p = 0.82), or retinal sensitivity (+3.3 versus +4.1 dB, p = 0.67). CONCLUSION: In treatment-naïve BRVO patients, addition of navigated central laser to aflibercept did not lower treatment burden or affect functional or anatomical outcomes. A low number of intravitreal injections were needed for successful outcome in both treatment arms.

Pretraining of basic skills on a virtual reality vitreoretinal simulator: A waste of time.

PURPOSE: To investigate whether pretraining of basic skills in virtual vitreoretinal surgery affected the performance curve when proceeding to procedure-specific modules. METHODS: This study was a prospective, randomized, controlled, two-centre study. Medical students were randomized into two groups: Group 1 pretrained basic psycho-motor skills (Navigation Training level 2 and Bimanual Training level 3) until they reached their performance curve plateau. Hereafter, both groups trained on the procedure-specific modules (Posterior Hyaloid level 3 and ILM Peeling level 3) until they reached their performance curve plateau. Plateau was defined as three consecutive sessions with the same score with an acceptable variation. The primary outcome was time used to reach performance curve plateau in the procedure-specific modules. RESULTS: A total of 68 medical students were included, and equally randomized into two groups. The participants in Group 1 used a median time of 88 minutes to reach plateau in the basic skills modules but did not differ from Group 2 in time to reach plateau on the procedure-specific modules (183 min versus 210 min, p = 0.40) or in the amplitude of plateau. Group 1 and 2 differed significantly in the starting score of ILM peeling level 3 (0 (0-0) versus 3.5 (0-75), p = 0.03). CONCLUSION: We were not able to show positive skill transfer from basic skills training to the procedure-specific modules in time, starting score or amplitude of plateau. Thus, we recommend that aspiring vitreoretinal surgeons proceed directly to simulation-based training of procedures instead of spending valuable training time on basic skills training.

Retinal vascular oxygen saturation in response to a less extensive laser treatment in proliferative diabetic retinopathy.

PURPOSE: The purpose of this study was to evaluate the association between retinal laser burden and vascular oxygen saturation in patients with proliferative diabetic retinopathy (PDR) treated with different extent of retinal laser. METHODS: The study was a prospective, interventional study of patients with treatment-naïve PDR. Patients were treated with navigated retinal laser (Navilas® , OD-OS GmbH, Teltow, Germany) in different doses. Retinal oximetry was obtained at baseline (BL) prior to laser and after 6 months (M6). Patients were divided into three groups according to total laser spots applied: <1500 spots (Group 1), 1500-2000 spots (Group 2), and >2000 spots (Group 3). RESULTS: We included 33 eyes of 28 patients with treatment-naïve PDR. The groups did not differ according in BL characteristics. Between BL and M6, retinal arteriolar oxygen saturation did not change but retinal venular oxygen saturation (median with interquartile range) decreased in Groups 1 and 2 (1: 65.5 ± 8.8% versus 60.5 ± 9.5%, p = 0.04; 2: 65.3 ± 7.3% versus 63.0 ± 13.5%, p = 0.04). Focal retinal venular oxygen saturation, located to quadrants with retinal neovascularization, decreased in Group 2 from BL to M6 (67.5 ± 13.3% versus 61.5 ± 8.8%, p = 0.04). Retinal venular diameter decreased from BL to M6 in Group 1 (174.5 ± 15.3 µm versus 165.1 ± 28.7 µm, p = 0.01). CONCLUSIONS: In this study of patients with treatment-naïve PDR, we showed that a less extensive laser treatment caused a reduction in retinal venular oxygen saturation and diameter 6 months after treatment. Our results suggest that less extensive laser treatment may be sufficient to improve the retinal metabolic environment conducive to PDR regression.

Optical coherence tomography angiography measured area of retinal neovascularization is predictive of treatment response and progression of disease in patients with proliferative diabetic retinopathy.

BACKGROUND: The purpose of this study was to evaluate the area of retinal neovascularization in patients with treatment-naïve proliferative diabetic retinopathy (PDR) as measured by optical coherence tomography angiography (OCT-A) as a marker of subsequent treatment response after panretinal photocoagulation (PRP), and to examine if this area correlated with area of retinal neovascularization as measured by fluorescein angiography (FA). METHODS: En face OCT-A scans (4.5 × 4.5 mm) of neovascularizations were obtained at baseline (BL) before PRP and at month (M) 3 and M6 after treatment. Progression of PDR were defined as lesion growth (assessed by ophthalmoscopy and wide-field fundus photo) or increasing leakage by Optos ultra-widefield FA, and patients were divided into two groups; progression or non-progression. Mann-Whitney U test and Wilcoxon signed-rank test were used to analyse differences between groups and between time points. Areas of retinal neovascularizations (OCT-A and FA) were calculated by algorithms developed in Python (version 3.6.8, The Python Software Foundation, USA). RESULTS: Of 21 eyes included, 14 had progression of disease. Median OCT-A area did not differ between the two groups (progression vs. non-progression) at BL (76.40 ± 162.03 vs. 72.62 ± 94.15, p = 0.43) but were statistically significantly larger in the progression group at M6 (276.69 ± 168.78 vs. 61.30 ± 70.90, p = 0.025). Median FA area did not differ in the progression vs. the non-progression group at BL (111.42 ± 143.08 vs. 60.80 ± 54.83, p = 0.05) or at M6 (200.12 ± 91.81 vs. 123.86 ± 162.16, p = 0.62). Intraclass correlation between area by OCT-A and FA was -5.99 (95% CI: -35.28-0.993), p = 0.71. CONCLUSIONS: In this study of patients with treatment-naïve PDR, we showed that increasing area of retinal neovascularizations measured by OCT-A at M6 indicated progression of disease after PRP treatment. Our results suggest that area by OCT-A reflects disease activity and that it can be used as an indicator to monitor the progression of PDR over time, and to evaluate treatment response six months after PRP. Trial registration https://clinicaltrials.gov (identifier: NCT03113006). Registered April 13, 2017.

Changes of visual fields in treatment of proliferative diabetic retinopathy: a systematic review.

The aim of this systematic review was to compare certain side-effects [visual fields (VF), dark adaptation, colour vision (CV) and contrast sensitivity (CS)] of conventional panretinal photocoagulation (PRP) with those of other treatments in proliferative diabetic retinopathy (PDR). A systematic literature search was conducted on 30 November 2018 in PubMed and Embase. The search comprised the keywords 'proliferative diabetic retinopathy', 'laser', 'treatment' and 'anti-vegf'. We included prospective studies and randomized controlled trials that investigated certain side-effects (VF, dark adaptation, CV, CS) in treatment of PDR (primary outcome). In total, 1867 articles were screened, and 10 studies were included (2176 eyes of 2086 patients examined in the VF studies and 1360 eyes of 1360 patients examined in the CV and CS studies). Visual fields (VF) were investigated in 10 studies, CV in one study and CS in one study. Treatment modalities included conventional PRP, other modalities of laser treatment and vascular endothelial growth factor (VEGF) inhibitors. Four studies demonstrated a worse VF impact of PRP than VEGF inhibitors. Seven studies reported of an overall worsening in VF after laser with no differences between different laser approaches. No differences were found in CV or CS. Overall, we found a trend, confirmed in four large studies, towards VEGF inhibitors causing less harm to VF compared to conventional PRP. Whilst VF was generally depressed after laser, it did not differ between different treatment approaches. Furthermore, it was not possible to make certain conclusions of CV or CS, with only one study in each field.

[Simulation-based training in ophthalmologic surgery].

Over the past few decades, simulation-based training has become an increasingly widespread learning tool for training in medical procedures. This type of training provides the opportunity to learn in a safe simulation-based environment, where both technical and diagnostic skills can be developed. In Denmark, there has been developed evidence for simulation-based training in ophthalmology in cataract and vitreoretinal surgery. This form of evidence-based training is meaningful for real clinical setting, and in this review, we argue, that is important to apply for all medical fields.

Virtual vitreoretinal surgery: effect of distracting factors on surgical performance in medical students.

PURPOSE: We aimed to investigate the effect of four distracting factors on surgical performance in virtual vitreoretinal surgery. METHODS: Nineteen novice surgeons completed a validated training programme on the Eyesi surgical simulator (VRmagic GmbH, Manheim, Germany; software version 2.9.2) until a calculated target score was reached. The training programme consisted of four modules: navigation level 2 (Nav2), bimanual training level 3 (BimT3), posterior hyaloid level 3 (PostH3) and internal limiting membrane peeling level 3 (ILMP3). When properly trained, the participants completed the training programme once without distraction to generate reference scores and times. Next, they conducted the training programme under the influence of each of the following: auditory distraction, 12 hr of fasting, interrupted sleep and 24 hr of sleep deprivation. Wilcoxon signed-rank test was used to compare the distraction-induced results to the participants' reference scores and times. RESULTS: As compared to reference score (328), a lower performance was found for all four distractions: auditory distraction (289, p = 0.0012), fasting (302, p = 0.02), sleep interruption (304, p = 0.02) and sleep deprivation (300, p = 0.0006). In particular, PostH3 performance was influenced by all four interventions. (86 versus 50, p = 0,0012, 65, p = 0.05, 72, p = 0.05, 54, p = 0.0007 respectively). CONCLUSIONS: Virtual vitreoretinal surgery is an important tool for practicing complex surgical skills without compromising patient safety. In this study, deleterious effects on surgical performance were induced by four independent distracting factors. This knowledge is useful to optimize surgeons' work conditions and ensuring the best possible treatment of patients.

Simulation training in vitreoretinal surgery: a systematic review.

BACKGROUND: The purpose of this study was to perform a systematic review of the current literature on simulator-based training in vitreoretinal surgery (VRS). We examined the results regarding simulated VRS and provided an overview of how the current results may be employed in VRS training. Lastly, we evaluated the quality of these results. METHODS: The databases of Pubmed, Embase and Cochrane Library were searched for articles in English involving simulated VRS training. A qualitative analysis was performed, since the studies which met our inclusion criteria did not allow for a quantitative meta-analysis. RESULTS: We identified 203 articles of which seven met the inclusion criteria. Of these, six studies investigated simulation with EyeSi® Surgical (VRMagic, Mannheim, Germany). Six studies reported positive performance curves. Four studies showed construct validity. One study attempted to show skill transfer from simulator to vitrectomies performed on cadavers. Methodological quality of the included studies was moderate but lacking in instrument validation. CONCLUSION: Simulator-based training in VRS can assess and possibly assist acquisition of a variety of VRS skills. Further research is needed to support transfer from simulator to operating room. Future studies should strive to follow established validation frameworks and streamline study designs.

Optical coherence tomography angiography and microvascular changes in diabetic retinopathy: a systematic review.

To use optical coherence tomography angiography (OCTA) to evaluate foveal microvascular changes in diabetes by comparing the area of foveal avascular zone (FAZ) in healthy controls and patients with diabetes with no diabetic retinopathy (NDR) as well as different stages of diabetic retinopathy (DR). A systematic literature search was performed based on the population, intervention, comparison and outcome (PICO) strategy by two independent reviewers. The search was performed in PubMed, Embase and Cochrane Library, including keywords 'diabetes mellitus', 'DR' and 'OCTA'. Of 358 studies initially identified, 215 studies were screened after duplicate removal. Of these, we included 12 (nine cross-sectional and three retrospective) studies in this review. With the data at hand, it was not possible to perform a meta-analysis. The selected studies included patients with NDR (n = 8), non-proliferative diabetic retinopathy (NPDR, n = 8) and proliferative diabetic retinopathy (PDR, n = 6). Several of the studies provided information for more than one diabetic group. In general, there was a trend towards a larger area of FAZ in patients with diabetes. As compared to healthy controls, this was reported in patients with NDR (five of eight studies), NPDR (seven of eight studies) and PDR (six of six studies). Optical coherence tomography angiography (OCTA) is non-invasively able to identify foveal capillary non-perfusion as an early event in DR. In some studies, this has even been identified in patients without clinically identifiable microvascular lesions. Longitudinal studies would be needed to examine if OCTA-findings are able to predict long-term structural and functional outcome.

Heritability of Retinal Vascular Fractals: A Twin Study.

Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation. Results: The mean fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined. Conclusions: In young adult twins, the branching pattern of the retinal vessels demonstrated a higher structural similarity in monozygotic than in dizygotic twin pairs. The retinal vascular fractal dimension was mainly determined by genetic factors, which accounted for 54% of the variation. The genetically predetermination of the retinal vasculature may affect the retinal response to potential vascular disease in later life.

Noninvasive Retinal Markers in Diabetic Retinopathy: Advancing from Bench towards Bedside.

The retinal vascular system is the only part of the human body available for direct, in vivo inspection. Noninvasive retinal markers are important to identity patients in risk of sight-threatening diabetic retinopathy. Studies have correlated structural features like retinal vascular caliber and fractals with micro- and macrovascular dysfunction in diabetes. Likewise, the retinal metabolism can be evaluated by retinal oximetry, and higher retinal venular oxygen saturation has been demonstrated in patients with diabetic retinopathy. So far, most studies have been cross-sectional, but these can only disclose associations and are not able to separate cause from effect or to establish the predictive value of retinal vascular dysfunction with respect to long-term complications. Likewise, retinal markers have not been investigated as markers of treatment outcome in patients with proliferative diabetic retinopathy and diabetic macular edema. The Department of Ophthalmology at Odense University Hospital, Denmark, has a strong tradition of studying the retinal microvasculature in diabetic retinopathy. In the present paper, we demonstrate the importance of the retinal vasculature not only as predictors of long-term microvasculopathy but also as markers of treatment outcome in sight-threatening diabetic retinopathy in well-established population-based cohorts of patients with diabetes.