Management Of Diabetic Macular Edema Research Articles

Management of Diabetic Macular Edema: Guidelines from the Emirates Society of Ophthalmology.

In the United Arab Emirates, retinopathy has been shown to be present in 19% of the diabetic population, with diabetes identified in up to 40% of individuals aged over 55 years. Despite the prevalence of diabetic retinal diseases, there are no unified national guidelines on the management of diabetic macular edema (DME). These published guidelines are based on evidence taken from the literature and published trials of therapies, and consensus opinion of a representative expert panel with an interest in this condition, convened by the Emirates Society of Ophthalmology. The aim is to provide evidence-based, clinical guidance for the best management of different aspects of DME, with a special focus on vision-threatening diabetic retinopathy. Treatment should be initiated in patients with best-corrected visual acuity 20/30 or worse, and/or features of DME as seen on optical coherence tomography (OCT) with central retinal thickness (CRT) of at least 300 μm or in symptomatic patients with vision better than 20/25, and/or CRT less than 300 μm where there are OCT features consistent with center-involving macular edema. The treatment of DME is effective irrespective of glycated hemoglobin (HbA1c) level, and treatment must not be denied or delayed in order to optimize systemic parameters. All ophthalmic treatment options should be discussed with the patient for better compliance and expectations. Non-center-involving DME can be initially observed until progression toward the center is documented. Macular laser no longer has a primary role in center-involving DME, and anti-vascular endothelial growth factor (anti-VEGF) therapy should be considered as first-line treatment for all patients, unless contraindicated. If anti-VEGF is contraindicated, a steroid dexamethasone implant can be considered for first-line treatment. Recommendations for the treatment of DME in special circumstances and in relapsing and refractory DME are also discussed.

Economic Aspects in the Management of Diabetic Macular Edema in Italy.

BackgroundDiabetic Macular Edema (DME) is the most common cause of vision loss in diabetic patients. Currently, the Vascular Endothelial Growth Factor inhibitors (anti-VEGFs) are used as the first line of DME treatment and corticosteroid implants are usually used as a second-line treatment. These implants are a safe and effective therapeutic option that can improve the quality of life of DME patients by reducing the intravitreal injections number. We determined the economic impact related to DME, also from the social perspective, and the consequences of the increased use of the dexamethasone implant.MethodsThe analysis compares two scenarios: the first based on the current rate of recourse to the therapeutic alternatives available in the Italian healthcare setting (as is) and the second based on the assumption of an increased recourse to dexamethasone implants (to be). The results are expressed both in terms of the resource absorption associated with the two scenarios and in terms of the cost differential yielded by their comparison.ResultsThe increased use of the dexamethasone implant allows considerable savings in terms of healthcare professionals' time, follow-up and productivity lost by patients/caregivers. These savings would reduce healthcare costs for the management of DME patients in Italy by €2,058,238 in 5 years.ConclusionsTo optimize the healthcare resources allocation, it is necessary to implement treatments that yield not only cost reductions but also a clinical benefit for patients. The dexamethasone implant use is an example of DME management that generates value for patients, health system and society.

Comparison of Suprachoroidal Injection of Triamcinolone Acetonide Versus Intravitreal Bevacizumab in Primary Diabetic Macular Odema

Objective: Present study aims to compare the efficacy of single dose triamcinolone acetonide suspension in suprachoroidal space and intravitreal bevacizumab in primary diabetic macular edema patients. Study design: Prospective observational study Study duration and settings: Study was conducted at department of ophthalmology, Eye Unit III, Mayo hospital Lahore (KEMU) from March 2020 to August 2020. Material and methods: The WHO calculator was used to estimate a sample size of 136 patients (66 patients in each group). Non-probability sequential sampling was used to identify patients.. Intravitreal bevacizumab injections (2.5 mg/0.1 mL) were given to patients in Group A, and triamcinolone acetonide was given to patients in Group B, all at random. After one and three months, patients were reassessed. Results: Total 135 patients were included in study. There were 71(52.2%) male and 65(47.8%) female. Mean age of patients was 41.1±6.9SD. BCVA improved 5 letters after 3 month was significantly high in TA group as compared to IVB (P=0.002). Moreover, CSF decreased at least 10% from baseline after one and three months was comparatively high in TA group (p=0.01 and p=0.04 respectively). Among all the patients in IVB group, 29.5% showed efficacy while in group TA, 37.5% showed efficacy (p=0.03) Conclusion: Triamcinolone acetonide is an efficient drug for management of diabetic macular edema. Triamcinolone had long standing effect as compared to intravitreal bevacizumab on structural and functional outcome of the patients with primary diabetic macular odema. Both interventions are associated with limited complications. Keywords: Triamcinolone acetonide, Diabetic macular edema, Intravitral bevacizumab

Efficacy of Intravitreal Triamcinolone Acetonide in Diabetic Macular Edema

Diabetic macular edema (ME) can be treated by intravitreal injection of Triamcinolone acetonide (TA). The scope of the study was to determine its efficacy in our setup in order to develop our local guidelines for its routine use in our setup. Objective: To determine the effect of intravitreal Triamcinolone(TA) for the management of diabetic macular edema(ME) Material and Methods: This descriptive case series carried out at Al-Shifa Trust Eye Hospital, Rawalpindi in 2019. Total 149 patients cases of either gender aged 40-75 years with history of DM of >10 years, VA<6/36 assessed by Snellen VA chart and who had clinically significant ME as assessed by indirect ophthalmoscopy were included in the study. 4mg/0.1 ml of TA was injected through pars plana under local anesthesia. Efficacy was determined at six week post treatment. Results: Treatment was found to be effective in overall 40.9%(n=61) cases, 44.7%(n=38) males, 35.9%(n=23) were females, 35.1%(n=20) were between 41-50 years age, 42.9%(n=30) between 51-60 years, 50%(n=11) had >60 years, 44.5%(n=49) at baseline VA of 6/36 and 30.8%(n=12) with baseline VA of 6/60 showed improvement in VA. Conclusion: Administration of triamcinolone acetonide(TA) intravitreal inj. is an effective modality for the treatment for diabetic macular edoema, and this treatment may lead to an improvement in visual acuity Keywords: Diabetic Retinopathy, Macular Edema(MA), Triamcinolone, Acetonide

Comparative Study between Intravitreal Ranibizumab Injection and Subthreshold Micropulsed Diode Laser (DSM) in Management of Diabetic Macular Edema

Comparative Study between Intravitreal Ranibizumab Injection and Subthreshold Micropulsed Diode Laser (DSM) in Management of Diabetic Macular Edema

Treatment of diabetic macular edema in real-world clinical practice: The effect of aging.

ABSTRACTAims/IntroductionIn older patients, the management of diabetic macular edema (DME) can be complicated by comorbidities, geriatric syndrome, and socioeconomic status. This study aims to evaluate the effects of aging on the management of DME.Materials and MethodsThis is a real‐world clinical study including 1,552 patients with treatment‐naïve center‐involved DME. The patients were categorized into 4 categories by age at baseline (C1, <55; C2, 55–64; C3, 65–74; and C4, ≥75 years). The outcomes were the change in logarithm of the minimum angle of resolution best‐corrected visual acuity (logMAR BCVA) and central retinal thickness (CRT), and the number of treatments from baseline to 2 years.ResultsFrom baseline to 2 years, the mean changes in logMAR BCVA from baseline to 2 years were −0.01 in C1, −0.06 in C2, −0.07 in C3, and 0.01 in C4 (P = 0.016), and the mean changes in CRT were −136.2 μm in C1, −108.8 μm in C2, −100.6 μm in C3, and −89.5 μm in C4 (P = 0.008). Treatments applied in the 2 year period exhibited decreasing trends with increasing age category on the number of intravitreal injections of anti‐VEGF agents (P = 0.06), selecting local corticosteroid injection (P = 0.031), vitrectomy (P < 0.001), and laser photocoagulation outside the great vascular arcade (P < 0.001).ConclusionsCompared with younger patients with DME, patients with DME aged ≥75 years showed less frequent treatment, a lower BCVA gain, and a smaller CRT decrease. The management and visual outcome in older patients with DME would be unsatisfactory in real‐world clinical practice.

Clinical Relevance of Body Fluid Volume Status in Diabetic Patients With Macular Edema.

ObjectiveTo investigate body fluid status in diabetic macular edema (DME) patients and the extent to which it is affected by renal function.MethodsOne hundred and thirty-two eyes from 132 patients with diabetes mellitus (DM) were prospectively collected in this cross-sectional, observational study. Thirty-five were DM patients without diabetic retinopathy (DR), 31 were DR patients without DME, and 66 were DME patients. The fluid status of each participant was quantified with extracellular water-to-total body water ratio (ECW/TBW) using a body composition monitor. Central subfield thickness (CST) and macular volume (MV) were obtained using optical coherence tomography (OCT). Urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and albumin was obtained using serum and urine laboratory data.ResultsECW/TBW was significantly increased in DME patients (39.2 ± 0.9, %) compared to DM (38.1 ± 0.7, %, P = 0.003) and DR patients without DME (38.7 ± 0.9, %, P < 0.001). In multilinear regression, fluid overload was positively related to DME and UACR (DME vs. DM: β = 2.418, P < 0.001; DME vs. DR: β = 1.641, P = 0.001; UACR, per 102, β = 1.017, P = 0.01). In the binary logistic regression for DME risk, the area under the receiver operating characteristic curve (AUROC) increased significantly by adding ECW/TBW along with UACR and age (AUC: 0.826 vs. 0.768).ConclusionDME patients had elevated body fluid volume independent of kidney functions. The assessment of extracellular fluid status may help in the management of DME.

IDF21-0299 An automatic deep learning-based system for screening and management of DME

Background: Diabetic macular oedema (DME) is the most common complication form of sight-threatening retinopathy in people with a diabetic condition. Previous studies demonstrate specifically that poor glycaemic and blood pressure control are associated with the presence and development of DME condition. The aim of this study is to validate the implementation of deep learning systems as a tool into routinely practiced diabetic retinopathy screening to improve diagnosis and management of DME. Method: 62,383 color images of the eye fundus were used. These images were acquired between 2016 and 2020 with a non mydriatic Centervue DRS camera. Images were graded as DME and no DME by retinal specialists according to the classification of American Association of Ophthalmology. The dataset was randomly divided into train-validation and test sets in proportions of 89.5% and 10.5%, respectively. We trained 4 CNNs based on the ResNeXt architecture with standardised convolutions as in Kolesnikov et al (ECCV 2020). Model parameters were initialized from a solution to the ImageNet image classification task and further optimized by minimizing the cross-entropy loss in its Sharpness-Aware extension, which attempts to find a parameter configuration lying in neighborhoods with uniformly low loss values, leading to improved generalization ability. The training was carried out by error back-propagation with weight updates given by the Stochastic Gradient Descent algorithm, and a learning rate of 0.01 that was cyclically annealed towards 0. The optimization ran for 20 cycles but was stopped as soon as the AUC computed on the validation set did not improve for two cycles. Final predictions were computed from the average ensemble of the four models. Results: The resulting model obtained a high performance on the test dataset. The area under the curve (AUC) was 0.9591(0.9536-0.9645). In addition, at an optimal cut-off given by the Youden index, the accuracy, the sensitivity and the specificity achieved were 0.9033(0.8959-0.9104), 0.8942 and 0.9054 respectively. An F1 score of 0.7759 and a Kappa score of 0.7156 indicate a high agreement of the model’s predictions with ophthalmologists’ opinions. Conclusion: The proposed system achieved high sensitivity and specificity in DME screening from retinal images of the eye fundus. The performance of the proposed approach is comparable to that of human experts and could be a valuable tool to help primary care triage.

Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)

Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA)

Exploring the Mechanism of Wu Ling San plus Flavor for the Treatment of Diabetic Macular Edema Based on Network Pharmacology and Molecular Docking Techniques

Aim: To explore the possible mechanism of action of Wu Ling San Plus for the treatment of diabetic macular edema (DME) through network pharmacology and molecular docking. Methods: DME-related genes were searched in drugbank database, GeneCards database, Online Mendelian Human Genetic (OMIM) database, and TTD database. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was applied to screen for potential chemically active substances and related target proteins in the drug pairs. A “drug-disease target” regulatory network was constructed with Cytoscape (3.7.2) software, and a protein-protein interaction (PPI) network was established by Bisogenet and CytoNCA, followed by GO and KEGG enrichment analysis using the Bioconductor platform and R software. Finally, molecular docking of potential chemically active substances and key targets was performed using MOE software. Results: 63 compounds were screened from Wu Ling San Plus, including 71 targets for the treatment of DME, and the PPI core genes were AKT1, JUN, TP53, IL10, VEGFA, IL6, MMP9, CASP3, CCL2, PTGS2, MAPK8; GO biofunctional analysis contained 2143 enrichment results, mainly involving the hypoxic responses, the KEGG enrichment yielded 122 related signaling pathways consisting of the AGE-RAGE signaling pathway, cellular senescence pathway, TNF signaling pathway, IL-17 signaling pathway, C-type lectin receptor signaling pathway, FoxO signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway, etc. Molecular docking results indicated that quercetin may have an effect on AKT1, TPP53, VEGFA, IL6, MMP9, CASP3, CCL2, PTGS2, and kaempferol also had a better binding ability to MAPK8. Conclusion: The treatment of DME with Wu Ling San Plus shows the multi-component and multi-target features of traditional Chinese medicine, which may achieve the management of DME’s developing process through many routes, offering certain insights and a foundation for further research.

Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab\u2014retinal layers thickness as prognostic biomarkers

To evaluate the role of the vitreous in the management of diabetic macular edema with ranibizumab intravitreal injections in a pro re nata regimen. Prospective study of 50 consecutive eyes with diabetic macular edema treated with ranibizumab and 12 months of follow-up. Primary endpoint: to assess differences between non-vitrectomized and vitrectomized eyes in the number injections needed to control the edema. Secondary endpoints: comparison of groups regarding best corrected visual acuity, central foveal thickness and thickness of seven retinal layers. 46 eyes from 38 patients, 10 vitrectomized and 36 non-vitrectomized, completed the follow-up. At month 12, the two groups achieved an equivalent anatomical outcome and needed a similar number of ranibizumab intravitreal injections. In vitrectomized eyes final visual acuity was worse when baseline retinal nerve fiber layers in the central foveal subfield were thicker, showing a strong correlation (r = − 0.942, p < 0.001). A similar, albeit moderate correlation was observed in non-vitrectomized eyes (r = − 0.504, p = 0.002). A decrease of retinal nerve fiber layers inner ring thickness was correlated with a better final visual acuity only in vitrectomized eyes (r = 0.734, p = 0.016). The effect of diabetic macular edema seems to be worse in vitrectomized eyes, with a thinner inner retina reservoir.Clinicaltrials.govNCT04387604.

Recommendations for the management of diabetic macular oedema with intravitreal dexamethasone implant: A national Delphi consensus study.

The intravitreal dexamethasone implant (DEX-I) is an alternative to anti-VEGF for the first-line treatment of diabetic macular oedema (DME). However, several questions remain regarding its routine use and its place in certain situations not always specified in current recommendations. A national consensus approach was, therefore, initiated by French retinal experts. An iterative Delphi consensus approach was used. A steering committee (SC) of seven experts analysed data from the literature to formulate statements divided into five key areas of treatment. These statements were submitted to the independent and anonymous electronic vote of 87 French retina experts among whom 39 expressed their opinion and therefore constituted the voting panel. After two rounds of voting, 22 and 7 of 38 statements received a strong consensus and a good consensus, respectively. The consensus level was higher for statements regarding first-line indications and safety of DEX-I compared to those regarding efficacy assessment, reprocessing time or pathophysiological biomarkers. The panellists recommended the preferential use of DEX-I for patients with limited availability for multiple injections, those who needed to undergo cataract surgery or who had a recent cardiovascular history, and as a therapeutic alternative to anti-VEGF in patients with a history of vitrectomy, retinal serous detachment, hyper-reflective points or dry exudates in optical coherence tomography (OCT). However, some statements proposed by SC experts were not validated. This study provides some key recommendations to clinicians treating diabetic macular oedema, which may be useful when using intravitreal dexamethasone implants in daily practice.

OCT-based biomarkers for predicting treatment response in eyes with centre-involved diabetic macular oedema treated with anti-VEGF injections: a real-life retina clinic-based study

Background/aimsTo determine whether a combination of baseline and change in spectral domain-optical coherence tomography (SD-OCT)-based biomarkers can predict visual outcomes in eyes with diabetic macular oedema (DMO) treated with antivascular...

The AflibeRcept use in rEal life study for the treatment of diabetiC macular oedema In the French overseas territories: A 12 months follow-up Study - The RECIF Study.

The incidence and severity of diabetes is particularly high in the French overseas territories (FOT). The RECIF study evaluated real life management of diabetic macular oedema (DME) treated by aflibercept in FOT. A prospective, noncomparative, multicentric, non-interventional, study that evaluated functional and anatomical results of patients treated by aflibercept. Twelve retina specialists working in French Polynesia, La Reunion, Guadeloupe and Martinique participated in the study. 67 eyes of 57 patients were followed for 12 months. Average VA gain was 7.8 ETDRS letters. 29.9% of eyes gained at least 15 letters, 6% lost 15 letters or more. 67.2% of eyes achieved visual acuity of 70 letters or better. Average central retinal thickness decrease was 115.3 µm. The mean number of injections during the 1st year of treatment was 4.9. 69% of eyes had a loading dose of at least three-monthly injections. 3 eyes were switched to steroid injections during the follow-up for lack of efficacy. This study confirmed the efficacy of intravitreal treatment of DME by aflibercept, in the French overseas territories. This evaluation of real-life management of DME underlines the importance of improvement of patient education and collaboration with referring physicians.

Tofacitinib Ameliorates Retinal Vascular Leakage in a Murine Model of Diabetic Retinopathy with Type 2 Diabetes.

We have previously reported that inhibition of the Janus kinase 1 (JAK1) signaling ameliorates IL-17A-mediated blood-retinal barrier (BRB) dysfunction. Higher levels of IL-17A have been observed in the blood and intraocular fluids in patients with diabetic retinopathy (DR), in particular those with diabetic macular oedema. This study aimed to understand whether JAK1 inhibition could prevent BRB dysfunction in db/db mice, a model of type 2 diabetes (T2D). An in vitro study showed that high glucose treatment disrupted the junctional distribution of claudin-5 in bEnd3 cells and ZO-1 in ARPE19 cells and that tofacitinib citrate treatment prevented high glucose-mediated tight junction disruption. Albumin leakage, accompanied by increased levels of the phosphorylated form of JAK1 (pJAK1), was observed in three-month-old db/db mice. Treatment of two-and-a-half-month-old db/db mice with tofacitinib citrate for two weeks significantly reduced retinal albumin leakage and reduced pJAK1 expression. pJAK1 expression was also detected in human DR retina. Our results suggest that JAK1 inhibition can ameliorate BRB dysfunction in T2D, and JAK1 inhibitors such as tofacitinib citrate may be re-purposed for the management of diabetic macular oedema.

Role of Optical Coherence Tomography Angiography Imaging in Patients with Diabetes.

Ocular manifestations in patients with diabetes mellitus (DM) can present as microvascular changes. These microvascular changes can be challenging to identify on exams, and imaging technologies have commonly aided in the diagnosis and management of patients with DM. Optical coherence tomography angiography (OCTA) provides noninvasive image segmentation of various layers of the retina and choroid. Also, post-processing of images and associated quantitative measurements offer potential clinical enhancements. Our aim is to review the current evidence on the utility of OCTA for patients with DM. Research suggests OCTA to potentially provide potential clinical enhancements and alternative methods in detecting subclinical manifestation of diabetic retinopathy, staging diabetic retinopathy, management of diabetic macular edema, and monitoring of systemic markers in patients with diabetes mellitus. OCTA is a promising but relatively new modality, and differences in terminology, research designs, and image processing techniques provide a difficult landscape to navigate. Standardization within further validation is needed to determine the extent of OCTA's clinical utility, but the current literature suggests the potential for earlier detection of ocular manifestations in patients with DM, additional objective measurements for grading and management, and opportunity for additional biomarkers for treatment outcomes.

Intraocular Pressure Changes Are Predictive of Ocular Hypertension Onset After Fluocinolone Acetonide Implant: Significant Cutoffs and the Role of Previous DEX Implant.

Background: Fluocinolone acetonide (FAc) implant represents a long-term strategy for the management of diabetic macular edema (DME). Because of the 3-year duration, the careful monitoring of the intraocular pressure (IOP) is necessary. The main aim of the study was to provide quantitative IOP cutoffs associated with the onset of IOP increases.Methods: The study was retrospectively conducted with 2-year of follow-up. We separately considered eyes with good IOP control (Group 1), eyes requiring IOP-lowering medications (Group 2) and eyes undergoing IOP-lowering surgery (Group 3). The statistical analysis assessed Delta% IOP changes over the 2-year follow-up. ROC analysis was performed to detect significant cutoffs associated with Group 2 and Group 3. IOP changes occurring after a previously administered dexamethasone (DEX) implant were also evaluated.Results: We included 48 eyes (48 patients), stratified as follows: Group 1 (25/48; 52%), Group 2 (19/48; 40%) and Group 3 (4/48; 8%). ROC analysis performed on IOP values detected 2-months later DEX implant showed a mean Delta IOP increase>24% significantly associated with IOP-lowering medications after FAc implant, whereas a mean Delta IOP increase>35% was significantly associated with IOP-lowering surgery after FAc implant. With respect to IOP changes occurred after FAc implant, our ROC analysis showed a mean Delta IOP increase>8% significantly associated with IOP-lowering medications, whereas a mean Delta IOP increase>15% was significantly associated with IOP-lowering surgery. DEX-related IOP changes showed 52% sensitivity and 100% specificity of FAc-related IOP increases.Conclusions: IOP changes provides clinically relevant cutoffs associated with the onset of FAc-related IOP increases.

COMPARISON OF THE EFFECT OF RANIBIZUMAB AND TRIAMCINOLONE ACETONIDE IN DIABETIC MACULAR EDEMA WITH EPIRETINAL MEMBRANE IN PSEUDOPHAKIC PATIENTS

Background: Macular edema is considered the main cause of visual loss in diabetic retinopathy patients. Aim: The aim of this study is to compare the effectivness of Intravitreal Ranibizumab and Triamcinolone acetonide in management of diabetic macular edema with epiretinal membrane in pseudophakic patients. Methods: In this prospective observational study we compared the efficacy of Intravitreal Ranibizumab and Triamcinolone acetonide on 35 eyes of 28 pseudophakic patients with DME with ERM. BCVA , IOP and CMT were recorded to patients before injection and then at 1st , 4th , 8th and 12th week after injection. Results: BCVA improved from 0.5 (0.3–1.4) to reach 0.2 (0–0.9) LogMAR at 12th week postinjection in the Ranibizumab group and improved from 0.6 (0.5–1.6) to 0.4 (0.1–1.5) LogMAR at 12th week postinjection in TA group. IOP changed from baseline of 19.06±2.9 to 23.17±2.68 at 1st week reaching 19.56±1.72 at 12th week (p

Diabetic Retinopathy Clinical Research Retina Network Protocols in the Management of Diabetic Macular Edema

The Diabetic Retinopathy Clinical Research Network (DRCR) retina network was formed in 2002 through a United States National Eye Institute and National Institute of Diabetes and Digestive and Kidney Diseases-sponsored cooperative agreement with the objective of creating a collaborative network for multicenter clinical trials focusing on diabetic retinopathy (DR) and its associated complications. The DRCR Retina Network has initiated and completed 30 multicenter studies in over 350 clinical sites. The goals of the DRCR was to design, implement, and report clinical studies that would answer important questions related to clinical practice and management of DR as well as DME. Diabetic macular edema (DME) is the leading cause of vision loss in the working age population and until the turn of the century the treatment options were limited to macular laser. This review aims to summarize the major DME studies completed by the DRCR The current review covers the major clinical trials that have helped help establish the current standard of care in the management of DME including protocols A, B, I, T, U and V.

Laser in diabetic macular edema

Laser photocoagulation has been an integral part of the management of diabetic macular edema (DME) for decades. And despite the dramatic changes in retinal imaging and the availability of new treatment options over the years it is still has a role in the pharmacotherapy era. First, as a supplementary treatment in eyes with CI-DME inadequately responding to antiVEGFs and steroids; to reduce the number and frequency of injections. And secondly, it is the only scientifically proven option for eyes with non CIDME with CSME features.