Center-involved Diabetic Macular Edema Research Articles

Diagnostic Utility of Swept-Source OCT-Based Biometry and Fundus Photographs Compared to Spectral Domain OCT in Center-Involving Diabetic Macular Edema

ABSTRACT Purpose This study was aimed to evaluate the agreement between the swept-source optical coherence tomography (SS-OCT)-based biometry, fundus photographs, and their combination, in comparison to the gold standard spectral-domain optical coherence tomography (SD-OCT) for the detection of center-involving diabetic macular edema (CI-DME). Methods We conducted a retrospective cross-sectional study involving 55 subjects (78 eyes) diagnosed with diabetic macular edema (DME) detected clinically and on SD-OCT (Carl Zeiss Meditec AG). Post-mydriatic 45-degree color fundus photograph (Crystal-Vue NFC-700), 1 mm macular scan obtained from SS-OCT-based biometry (IOL-Master 700), and macula cube scan obtained from SD-OCT was used to detect and grade DME into CI-DME and NCI-DME. Results Our findings revealed that SS-OCT-based biometry was noted to have a high sensitivity of 1 (0.94–1.00) and a specificity of 0.63 (0.31–0.89) in detecting CI-DME compared to the gold standard (SD-OCT). When combined with data from fundus photographs, specificity decreased to 0.32 (0.15–0.53). Fundus photographs alone exhibited a low sensitivity of 0.52 (0.38–0.64) and a specificity of 0.45 (0.16–0.76) in CI-DME detection. Conclusion In conclusion, SS-OCT-based biometry can be used as an effective tool for the detection of CI-DME in diabetic patients undergoing cataract surgery and can serve as a screening tool in centers without SD-OCT facilities.

Characterization of central-involved diabetic macular edema using OCT and OCTA.

To characterize the occurrence of diabetic macular edema and the presence of abnormal retinal fluid accumulation in nonproliferative diabetic retinopathy (NPDR). In this two-year prospective study, a total of 122 eyes with diabetes type 2 underwent optical coherence tomography (OCT) and OCT-Angiography in association with OCT-Fluid imaging, a novel algorithm of OCT analysis allowing quantification of abnormal accumulation of fluid in the retina through low optical reflectivity ratios (LOR). Early Treatment Diabetic Retinopathy Study (ETDRS) grading for diabetic retinopathy (DR) severity assessment was performed using 7-field color fundus photography. Best corrected visual acuity was also recorded. During the 2-year follow-up, 23 eyes (19%) developed central-involved diabetic macular edema (CI-DME) and 2 eyes (2%) developed clinically significant macular edema (CSME). In the two-year period of the study, eyes that developed CI-DME showed a progressive increase in central retinal thickness (CRT) (β = 7.7 ± 2.1 µm/year, p < 0.001) and in LOR values (β = 0.009 ± 0.004 ratio/year, p = 0.027). The increase in CRT and abnormal retinal fluid, represented by increased LOR ratios, are associated with increased retinal perfusion in the deep capillary plexus (DCP) (skeletonized vessel density, p = 0.039). In contrast, the eyes with CSME showed decreased retinal perfusion and abnormal fluid located in the outer layers of the retina. CI-DME and CSME appear to represent different entities. Eyes with CI-DME show increases in abnormal retinal fluid associated with increased retinal vascular perfusion in the DCP. Eyes with CSME are apparently associated with decreased retinal vascular perfusion in the DCP and abnormal fluid in the outer retina.

Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy

Severity of Disorganization of Retinal Layers and Visual Function Impairment in Diabetic Retinopathy

Short-Term Effects of Adding Topical Ketorolac to Intravitreal Bevacizumab in Diabetic Macular Edema: A Crossover Randomized Clinical Trial.

To evaluate the short-term additive effects of topical ketorolac to intravitreal bevacizumab (IVB) in the management of center-involved diabetic macular edema (CI-DME). In a randomized double-masked placebo-controlled crossover clinical trial, eyes with CI-DME and the best-corrected visual acuity (BCVA) between (20/40) and (20/400) were included. These eyes should have had at least one intravitreal anti-VEGF injection in the preceding two months. They were randomized into two groups; while both groups received two IVB injections with a six-week interval, one group received topical ketorolac every 6 hr in the first interval and artificial tears every 6 hr as a placebo in the second interval and the other group received the same medications using a crossover method. The main outcome measures were changes in BCVA and central macular thickness (CMT). Fifty-seven eyes of 35 patients with CI-DME were included in the study. The mean BCVA improvement was -0.09 0.47 logMAR in the periods of receiving ketorolac and -0.03 0.12 logMAR in the periods of placebo treatment, respectively (P = 0.99). Corresponding changes in CMT were -13.1 170.1 and +11.7 157.7 µm in the ketorolac and placebo periods, respectively (P = 0.322). The treatment effect was not statistically significant regarding both BCVA and CMT changes. Statistical analysis also disclosed that the carryover effect was insignificant for BCVA and CMT. Although the period effect was not significant for BCVA, it was at a meaningful level for CMT changes (P = 0.012). This crossover clinical trial demonstrated that in the course of DME treatment with IVB injections, topical ketorolac did not have any additive beneficial effect at least during a six-week period.

Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial

A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO. PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503). Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]). Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO. Regeneron Pharmaceuticals and Bayer.

Topical Dorzolamide as Adjunctive Treatment With Intravitreal Bevacizumab in Bilateral Diabetic Macular Edema.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME. This prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center, Al-Zahra Eye Hospital, Zahedan, Iran, between April 2021 and April 2022. Thisstudy included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first three months. Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P > 0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P > 0.05). The present study showed a decrease in CMT in both study groups (P < 0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs. -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P < 0.001). The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline, but it did not have an additive effect on BCVA improvement compared to IVB monotherapy.

Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity of < 20/40

ObjectiveTo identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network Protocol AC. DesignPost hoc analysis of data from a randomized clinical trial Participants270 participants with one or both eyes with CI-DME and visual acuity (VA) letter score of 69 to 24 (Snellen equivalent 20/50-20/320) MethodsEligible eyes were assigned to receive intravitreal aflibercept monotherapy (N=158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (N=154). Main Outcome MeasuresMeeting switching criteria: 1) at any time, 2) at 12 weeks, and 3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. ResultsIn the bevacizumab first group, older participants had higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age (95% confidence interval) of 1.32 (1.11 – 1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (HR for male vs. female = 4.84 [1.32 – 17.81]; HR for 5-letter lower baseline VA: 1.30 [1.03 – 1.63]). Worse 12-week CST (HR for 10-μm greater = 1.06 [1.04 – 1.07]) was associated with increased risk for switching after 12 weeks. The mean (SD) improvement after completing the switch to aflibercept was 3.7 (4.9) letters. ConclusionsThe identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At twelve weeks, thicker central subfield thickness was predictive of eyes most likely to be switched in the future.

Consensus on managing center-involving diabetic macular edema in Hong Kong: perspective

Consensus on managing center-involving diabetic macular edema in Hong Kong: perspective

Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials

PurposeTo evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A pathway inhibition with intravitreal faricimab according to a personalized treat-and-extend–based regimen (T&E) with up to every-16-week (Q16W) dosing in the YOSEMITE/RHINE (NCT03622580/NCT03622593) phase 3 trials of diabetic macular edema (DME). DesignRandomized, double-masked, noninferiority phase 3 trials. ParticipantsAdults with visual acuity loss due to center-involving DME. MethodsPatients were randomized 1:1:1 to faricimab 6.0 mg Q8W, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg Q8W. The T&E up to Q16W dosing regimen was based on central subfield thickness (CST) and best-corrected visual acuity (BCVA) change. Main Outcome MeasuresIncluded changes from baseline in BCVA and CST, number of injections, durability, absence of fluid, and safety through week 100. ResultsIn YOSEMITE/RHINE (N=940/951), noninferior year 1 visual acuity gains were maintained through year 2; mean BCVA change from baseline at 2 years (weeks 92/96/100 average) with faricimab Q8W (YOSEMITE/RHINE, +10.7/+10.9 letters) or T&E (+10.7/+10.1 letters) were comparable with aflibercept Q8W (+11.4/+9.4 letters). The median number of study drug injections was lower with faricimab T&E (YOSEMITE/RHINE, 10/11 injections) versus faricimab Q8W (15 injections) and aflibercept Q8W (14 injections) across both trials during the entire study. In the faricimab T&E arms, durability was further improved during year 2, with >60% of patients on Q16W dosing and ∼80% on ≥Q12W dosing at week 96. Almost 80% of patients who achieved Q16W dosing at week 52 maintained Q16W dosing without an interval reduction through week 96. Mean CST reductions were greater, and more patients achieved absence of DME (CST <325μm) and absence of intraretinal fluid with faricimab Q8W or T&E versus aflibercept Q8W through year 2. Overall, faricimab was well tolerated, with a safety profile comparable to aflibercept. ConclusionsClinically meaningful visual acuity gains from baseline, anatomic improvements, and extended durability with intravitreal faricimab up to Q16W were maintained through year 2. Faricimab given as a personalized T&E–based dosing regimen supports the role of dual angiopoietin-2/VEGF-A inhibition to promote vascular stability and provide durable efficacy for patients with DME.

Optical coherence tomography angiography in diabetic retinopathy.

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR: Post Hoc Analysis of the PANORAMA Trial

PurposeIdentify baseline systemic and ocular characteristics associated with nonproliferative diabetic retinopathy (NPDR) worsening, and the impact of intravitreal aflibercept injection (IAI) on these associations. DesignPost hoc analysis of PANORAMA. ParticipantsPatients with moderately severe to severe NPDR enrolled in the prospective PANORAMA phase 3 trial. MethodsAssociations between baseline systemic and ocular factors with events indicative of NPDR worsening at Week 100 were evaluated by multivariable analysis in sham-treated eyes. NPDR worsening was defined as development of (1) vision-threatening complications (VTCs; comprising PDR and/or anterior segment neovascularization), (2) center-involved diabetic macular edema (CI-DME), or (3) ≥ 2-step Diabetic Retinopathy Severity Scale (DRSS) worsening. Impact of IAI on identified baseline factors was evaluated using univariable analysis in combined IAI groups. Main Outcomes MeasuresBaseline systemic and ocular factors associated with events indicative of NPDR worsening at Week 100. The cumulative incidence and risk of developing such events at Week 100 among sham versus IAI-treated eyes. ResultsUsing multivariable analyses among sham-treated eyes, 5 baseline factors associated with increased risk of NPDR worsening were identified: fluorescein leakage, retinal nonperfusion area, thicker central subfield thickness, eosinophil level, and proteinuria. Considering baseline fluorescein leakage area as a prognostic indicator in detail, the risk of developing VTCs alone, VTCs and/or CI-DME, or ≥ 2-step DRSS worsening increased with increasing fluorescein leakage area in the sham group (all P < 0.05). Considering baseline retinal nonperfusion area as a prognostic indicator in detail, the risk of developing VTCs alone, CI-DME alone, or VTCs and/or CI-DME increased with increasing baseline retinal nonperfusion area in the sham group (all P < 0.05). In contrast, among IAI-treated eyes, increasing baseline fluorescein leakage or retinal nonperfusion areas did not increase the risks of NPDR worsening. ConclusionsWithin the PANORAMA trial, increased areas of fluorescein leakage and retinal nonperfusion at baseline were identified as key ocular biomarkers associated with events indicative of NPDR worsening among sham-treated patients. IAI treatment appeared to mitigate the effect of these baseline risk factors and reduced the likelihood of NPDR worsening.

Comparison between intravitreal brolucizumab and aflibercept in the treatment-naive central involved diabetic macular edema: One-year real-life case series.

To evaluate the effectiveness and safety of intravitreal brolucizumab (IVB) and intravitreal aflibercept (IVA) injections in the management of naive central involved diabetic macular edema (CIDME). This study included 45 treatment-naive eyes with CIDME. A complete ophthalmic examination, including BCVA and SD-OCT was performed. Patients were randomized to (IVB) or (IVA) groups. All participants received a loading phase of three consecutive intravitreal injections, then followed by a personalized treat and extend (T&E) regimen. At 12-month follow-up, the mean numbers of injections in IVA and IVB groups were 7.25  ±  0.53 and 6.3  ±  0.45, respectively (P < 0.0001). The IVA group showed a significant increase of the mean BCVA from 0.66  ±  0.15 logMAR (50.9  ±  7.7 letters) to 0.41  ±  0.19 logMAR (63.7  ±  10.8 letters). Mean CFT decreased significantly from 441.2  ±  35.7 μm to 281.3  ±  18.4 μm. The IVB group showed a significant increase of mean BCVA from 0.65  ±  0.16 logMAR (52.1  ±  7.9 letters) to 0.39  ±  0.17 logMAR (65.3  ±  8.7 letters). Mean CFT decreased significantly from 437.2  ±  41.9 μm to 275.5  ±  21.7 μm.No significant difference between both groups in terms of the vision improvement and the reduction of CFT was reported, whereas a statistical difference was observed in terms of intravitreal injections (IVI) numbers. No ocular complications were reported. This case series highlights the effectiveness of both brolucizumab and aflibercept in the treatment of CIDME with a lower frequency of injection in brolucizumab group lowering the burden of IVI in this cohort.

OR2806 Levosulpiride-Induced Hyperprolactinemia For The Treatment Of Diabetic Macular Edema: A Phase 2 Pilot Clinical Trial

Abstract Disclosure: C. Clapp: None. C.D. Núñez-Amaro: None. M. López: None. E. Adán-Castro: None. M. Robles Osorio: None. R. García-Franco: None. M. García-Roa: None. Y. Villalpando: None. P. Ramírez-Neria: None. N. Pineiro: None. J.F. Rubio-Mijangos: None. J. Sánchez: None. G. Ramirez-Hernandez: None. L. Siqueiros-Márquez: None. N. Díaz-Lezama: None. E. López-Star: None. T. Bertsch: None. G. Martínez de la Escalera: None. J. Triebel: None. Vasoinhibin is a fragment of prolactin that inhibits the permeability and growth of blood vessels. The prokinetic dopamine D2 receptor blocker, levosulpiride, elevates the circulating levels of prolactin and the accumulation of vasoinhibin in the vitreous of patients with proliferative diabetic retinopathy (PDR) (1) suggesting clinical benefits due to the vascular properties of vasoinhibin. Here, we describe the 2-month results of a phase 2 clinical trial (2) investigating the biological activity of levosulpiride in center-involving diabetic macular edema (DME). This prospective, randomized, double-masked, dual-center, placebo-controlled, pilot study was carried out in individuals (aged 40 to 69 years) with DME involving the center of the macula and best-corrected visual acuity (BCVA) between 58 and 16 ETDRS letters at 4 m (20/16 to 20/100 Snellen equivalent) or with PDR undergoing elective pars plana vitrectomy. Oral treatment (TID) with levosulpiride or placebo was for 8 weeks in DME patients or for the 1 week before vitrectomy in PDR patients. Primary outcome measures included changes from baseline in BCVA, central foveal thickness (CFT), and mean macular volume (MMV) every 2 weeks for 8 weeks in placebo- (17 patients, 18 eyes) and levosulpiride- (17 patients, 22 eyes) treated DME groups; whereas vitreous levels of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were primary outcomes in PDR patients after placebo (18 patients) or levosulpiride (18 patients). Starting at 4 weeks, levosulpiride improved changes from baseline in BCVA (P &amp;lt; 0.037), CFT (P &amp;lt; 0.013), and MMV (P &amp;lt; 0.002) compared to placebo. At 8 weeks, the proportion of eyes gaining &amp;gt;5 letters (41% vs. 28%), loosing &amp;gt; 21 μm in CFT (55% vs. 28%), and dropping &amp;gt; 0.06 mm3 in MMV (65% vs. 29%) were higher in levosulpiride vs placebo. The overall grading of visual (BCVA) and structural parameters (CFT, MMV, OCT macula image, fundoscopy, and fluorescein angiography) showed improvement with levosulpiride (P = 0.029). Levosulpiride reduced VEGF (P = 0.025) and PlGF (P= 0.008) levels in the vitreous of PDR patients. There were no apparent adverse side-effects. In conclusion, oral levosulpiride administration for 8 weeks improved visual and structural outcomes in patients with center involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted. Reference: (1) Núñez-Amaro et al., Transl Vis Sci Technol. 2020 Aug 17;9(9):27. (2) www.clinicaltrials.gov, ID: NCT03161652; Supported by UNAM grant 405PC. Presentation: Sunday, June 18, 2023

Subthreshold micropulse laser versus standard laser for the treatment of central-involving diabetic macular oedema with central retinal thickness of

ObjectivesTo estimate the economic costs, health-related quality-of-life outcomes and cost-effectiveness of subthreshold micropulse laser (SML) versus standard laser (SL) for the treatment of diabetic macular oedema (DMO) with central retinal...

Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial

Background/ObjectiveThe prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME).Patients/MethodsProspective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy.ResultsLevosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 μm in CFT (55% vs. 28%), and dropping ≥0.06 mm3 in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected.ConclusionsOral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.

The psychological status of patients with delayed intravitreal injection for treatment of diabetic macular edema due to the COVID-19 pandemic.

Since the enforcement of the Movement Control Order (MCO) to contain the spread of COVID -19 infection in Malaysia, most clinic appointments have been rescheduled and procedures and surgeries postponed to a later date. Clinic appointments including intravitreal endothelial growth factor (anti-VEGF) treatment for patients with diabetic macular edema (DME) were also no exception to the postponement. This measure takes a psychological toll on patients because of the overwhelming concern for their eye condition. This study was conducted to assess the psychological status of DME patients with delayed anti-VEGF treatment during the pandemic. A cross-sectional study was conducted from September 2020 to March 2021 in Ophthalmology Clinic Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM). Subjects diagnosed with center-involved DME aged between 20 to 80 years who experienced delayed anti-VEGF injection were recruited. Level of depression, anxiety and stress were assessed using DASS-21 questionnaire. Statistical analysis using non-parametric tests were performed to determine the relationship between the DASS-21 score and duration of last injection, in those whose vision was affected by delayed injection and the relationship to the impact of COVID-19 pandemic. Statistical significance was denoted as p < 0.05. A total of 86 respondents with median age of 69 years old participated in this study. Most respondents were Malays (n = 47,54.7%) males (n = 51, 59.3%), had education up to secondary level (n = 37, 43%), unemployed (n = 78, 90.7%), married (n = 72, 83.7%) and living with their family (n = 82, 95.3%). The number of intravitreal injections received was at least three times among the respondents (n = 81, 94.2%). More than half of the respondents (n = 46, 53.5%) had been postponed for more than 12 weeks and felt that their vision was affected after delayed intravitreal injection (n = 47, 54.7%). Most of the subjects did not experience depression, anxiety, or stress. However, there was a significant level of stress scores among those with delayed injection of 9 to 12 weeks (p = 0.004), and significant anxiety (p = 0.029) and stress (p = 0.014) scores found in subjects with vision affected due to delayed treatment. The level of anxiety and stress can be significant in DME patients who experienced delay in intravitreal anti-VEGF treatment. Assessment of psychosocial impacts is important to identify early mental health issues potentially leading to the onset of psychiatry illness, thus early intervention is indispensable.

Retinal changes after fluocinolone acetonide implant (ILUVIEN®) for DME: SD-OCT imaging assessment using ESASO classification.

A detailed understanding of the anatomical and structural changes occurring in the retina following intravitreal fluocinolone acetonide implantation may help improve the management and prognosis of persistent or recurrent diabetic macular edema (DME). Overall, 45 eyes (from 35 patients) with refractory center-involved DME received an intravitreal fluocinolone acetonide implant. They were monitored at baseline and at 6, 12, 24, and 36 months for best-corrected visual acuity (BCVA), central foveal thickness (CFT), and the seven retinal parameters used in the classification of diabetic maculopathy recently developed at the European School for Advanced Studies in Ophthalmology (ESASO). Within 6 months of implantation, significant improvements were evident in BCVA, CFT, maculopathy stage, and the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent ellipsoid zone (EZ) and/or external limiting membrane (ELM). Significant improvements were still maintained at 36 months post-implantation. At month 36, early treatment with the implant (i.e., after < 6 previous intravitreal injections for DME) trended toward being more effective than later treatment in improving BCVA, CFT, maculopathy stage, and the percentage of eyes with CFT > 30% above the upper normal value. However, statistical significance was not achieved. In persistent or recurrent DME, fluocinolone acetonide implantation can be effective in improving maculopathy stage and reducing the percentage of eyes with: intraretinal cysts; CFT > 30% above the upper normal value; and disrupted or absent EZ and/or ELM. It can also increase BCVA and reduce CFT.

Distance and near vision changes after intravitreal anti-vascular endothelial growth factor injection in eyes with center-involving diabetic macular edema.

To elucidate distance and near vision changes after intravitreal injections in center-involving diabetic macular edema (CIDME) in phakic and pseudophakic groups. A retrospective study was done on 148 eyes (72 phakic and 76 pseudophakic) with center-involving DME. All eyes were treated with intravitreal anti-vascular endothelial growth factor (VEGF) injection. All patients underwent distance best-corrected visual acuity (BCVA) testing, near BCVA testing, dilated fundus examination, and optical coherence tomography (OCT) at baseline and follow-up visits. Eyes that could not improve after the first injection were given 2nd, 3rd, and more injections in the subsequent visits. On follow-up, post injections in the phakic group (n = 72), there were 65 eyes (90.3%) with stable/improved near vision and 59 eyes (81.9%) with stable/improved distance vision, whereas in the pseudophakic group (n = 76), 63 eyes (82.9%) and 60 eyes (78.9%), respectively. Both in phakic and pseudophakic eyes, 7.7%-13% of the cohort showed only near vision improvement. In DME, besides the changes in distance vision, there are also changes in near vision. These changes should be taken into account while determining the response to anti-VEGF in DME treatment.

Compliance with follow-up in patients with diabetic macular edema: Eye care center vs. diabetes care center.

The study was conducted to compare the compliance to intravitreal injection treatment and follow-up in patients with center-involving diabetic macular edema (CI-DME) and treatment outcomes between a tertiary eye care facility and a tertiary diabetes care center. A retrospective review was conducted on treatment naïve DME patients who had received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in 2019. Participants were people with type 2 diabetes who were under regular care at the eye care center or the diabetes care center in Chennai. The outcome measures were noted at months 1, 2, 3, 6, and 12. A review of 136 patients treated for CI-DME (72 from the eye care center and 64 from a diabetes care center) was carried out. The severity of diabetic retinopathy (DR) was similar in both centers. There was no statistically significant (P > 0.05) difference in the choice of initial intravitreal drug in the two centers. At 12-month follow-up, only 29.16% came for a follow-up in the eye center vs. 76.56% in a diabetes care center (P = 0.000). The multivariate logistic regression showed increasing age was associated with non-compliance in both the groups (eye care center: odds ratio [OR] 0.91; 95% confidence interval [CI] 0.82-1.21; P = 0.044) and diabetes care center (OR 1.15; 95% CI 1.02-1.29; P = 0.020). The follow-up rate between eye care and diabetic care center with DME showed a significant disparity. By providing comprehensive diabetes care for all complications under one roof, compliance with follow-up can be improved in people with DME.

Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema.

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.