Assessment of the predictive ability of theranostics for corneal cross-linking in treating keratoconus: a randomized clinical trial.

PURPOSE: To validate the ability of theranostic imaging biomarkers in assessing the propensity of corneal cross-linking (CXL) in flattening the maximum keratometry (Kmax) index. DESIGN: Prospective, randomized, multicenter, masked clinical trial (NCT05457647). PARTICIPANTS: Fifty patients with progressive keratoconus. INTERVENTION: Participants were stratified to undergo epithelium-off (epi-off; 25 eyes) and epithelium-on (epi-on; 25 eyes) CXL protocols using UV-A medical device incorporating theranostic software module. The device used controlled UV-A light both for performing CXL and for estimating the corneal riboflavin concentration (riboflavin score) and assessing treatment effect (theranostic score) in real time. A 0.22% riboflavin formulation was applied onto the cornea for 15 minutes and 20 minutes in epi-off and epi-on protocols respectively. All eyes underwent 9 minutes UV-A irradiance at 10 mW/cm2. MAIN OUTCOME MEASURES: The primary outcome measure was validation of the combined use of theranostic imaging biomarkers through measurement of their accuracy (proportion of correctly classified eyes) and precision (positive predictive value) to correctly classify eyes and positively predict a Kmax flattening at 1 year after CXL. Other outcome measures were the change of Kmax, endothelial cell density, uncorrected and corrected distance visual acuity, manifest spherical equivalent refraction, and central corneal thickness one year after CXL. RESULTS: Accuracy and precision of the combined use of theranostic imaging biomarkers in predicting eyes that had more than 0.1 diopter (D) Kmax flattening at 1 year were 91% and 95% respectively. The Kmax value significantly flattened by a median of -1.3 D (IQR: -2.11, -0.49 D; P < 0.001); both the uncorrected and corrected distance visual acuity improved by a median of -0.1 LogMAR (IQR: -0.3, 0.0 LogMAR; P < 0.001 and IQR: -0.2, 0.0 LogMAR; P < 0.001 respectively). There were no significant changes in endothelial cell density (P = 0.33) and central corneal thickness (P = 0.07) 1 year postoperatively. CONCLUSIONS: The study demonstrated the efficacy of integrating theranostics in a UV-A medical device for the precise and predictive treatment of keratoconus with epi-off and epi-on CXL protocols. The concentration of riboflavin and its UV-A light mediated photo-activation in the cornea are the primary factors determining CXL treatment efficacy.

A Novel Noninvasive Screening Tool for Dry Eye Disease.

PURPOSE: To assess the feasibility and the diagnostic accuracy of the new tool, DEvice© (AI, Rome, Italy), for screening patients with dry eye disease (DED). METHODS: This study was performed at the University Magna Græcia of Catanzaro. Enrolled patients were classified as affected by DED (group 1) or not (group 2) using an already validated tool (Keratograph 5M, Oculus, Germany), evaluating the noninvasive keratograph breakup time (NIKBUT), tear meniscus height (TMH), meibomian gland loss (MGL), and bulbar redness. All the patients were then examined by means of DEvice©, which allowed the measurement of the relative humidity (RH) and temperature of the ocular surface. Symptoms were scored using the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Overall, 40 patients (17 males and 23 females, mean age 38.0 ± 17.1 years) were included: of these, 20 belonged to group 1 and the remaining 20 to group 2. Using Keratograph 5M, significant differences between groups 1 and 2 were detected for NIKBUT-first (respectively, 4.97 ± 1.85 vs. 13.95 ± 4.8 s; p < 0.0001) and for NIKBUT-average (10.55 ± 4.39 vs. 15.96 ± 4.08 s; p = 0.0003). No statistically significant changes were detected for TMH (p = 0.565), MGL (p = 0.051), and bulbar redness (p = 0.687). Using Device©, a statistically significant higher value of RH was found in group 1 compared to group 2 (respectively, 85.93 ± 10.63 vs. 73.05 ± 12.84%; p = 0.0049). A statistically significant correlation was found between RH and OSDI (r = 0.406; p = 0.009). The value RH showed a discriminating power to detect DED with an AUC = 0.782 (standard error 0.07264; 95% CI 0.6401-0.9249; p = 0.0022). CONCLUSIONS: The DEvice© can effectively discriminate DED patients from healthy subjects. The parameter RH showed good sensitivity, making this tool ideal for a fast and noninvasive DED screening.

Petal-shaped corneal pattern in a patient with posterior amorphous corneal dystrophy.

Purpose: To describe the petal-shaped corneal pattern in a patient with posterior amorphous corneal dystrophy. Observation: A 19-year-old male affected by Graves' disease presented corneal grey sheet-like opacities and high hyperopia. Corneal topography showed reduced k-values compatible with cornea plana and reduced corneal pachymetry. The anterior segment optical coherence tomography showed a hyperreflective band at the posterior stroma-Descemet-Endothelium layers in both eyes. Slit lamp examination with cobalt blue filter showed a corneal pattern resembling a petal in right eye; the pattern was similar but incomplete in left eye. Conclusion & importance: After an exhaustive literature review conducted from October 1st to 30th, 2023, utilizing online databases like PubMed and Google Scholar, and employing keywords such as "Corneal Dystrophy," "Slit Lamp," "Cornea," and "Posterior Amorphous Corneal Dystrophy," we found no previous reports detailing the whole corneal pattern using a blue cobalt filter on the slit lamp in cases of posterior amorphous corneal dystrophy. Cobalt blue filter was an effective method for capturing the full photographic corneal pattern of the patient posterior amorphous corneal dystrophy.

Prospective Randomized Clinical Trial Evaluating Efficacy and Safety of A New Ophthalmic Viscosurgical Device In Patients Undergoing Cataract Surgery.

PURPOSE: To evaluate the efficacy and safety of Bio-Hyalur LVD compared to Viscoat® ophthalmic viscosurgical device (OVD) in patients undergoing routine cataract surgery. SETTING: Two tertiary eye care hospitals in Italy. DESIGN: Prospective randomized clinical trial. METHODS: This study compared the outcomes of Bio-Hyalur LVD versus Viscoat® ophthalmic viscosurgical device in patients undergoing standard cataract surgery with phacoemulsification and intraocular lens implantation from January 2021 to April 2022. The primary outcome was mean change in IOP at 6 hours. Secondary outcomes included 1-, 7-, 30- and 90-day mean intraocular pressure (IOP), 7-, 30- and 90-day best corrected visual acuity, endothelial cell density (ECD), change in central corneal thickness (CCT) and complications including intraocular inflammation. RESULTS: A total of 84 eyes of 84 patients (n = 41 in the Bio-Hyalur LVD group and n = 43 in the Viscoat group) were screened, enrolled, randomized, and included in the analysis. Mean change in IOP was significantly higher in the Viscoat group than in the Bio-Hyalur LVD group 6 hours (p = 0.034), 7 days (p < 0.001), 30 days (p < 0.001) and 90 days (p = 0.003) postoperatively. Mean change in UDVA and CDVA was significantly higher in the Bio-Hyalur LVD group 30 and 90 after surgery. No significant differences in ECD, CCT and complication rates were observed between groups at any time point. CONCLUSION: Bio-Hyalur LVD OVD is safe and effective for use in patients undergoing routine cataract surgery. Bio-Hyalur LVD OVD did not confer a higher risk of postoperative increase in IOP.

Targeted next-generation sequencing analysis in Italian patients with keratoconus.

OBJECTIVE: To report variants in 26 candidate genes and describe the clinical features of Italian patients with keratoconus (KC). SUBJECTS/METHODS: Sixty-four patients with a confirmed diagnosis of KC were enrolled in this genetic association study. Patients were classified into two study groups according to whether they had a confirmed diagnosis of progressive or stable KC. A purpose-developed Next Generation Sequencing (NGS) panel was used to identify and analyse the coding exons and flanking exon/intron boundaries of 26 genes known to be associated with KC and corneal dystrophies. Interpretation of the pathogenic significance of variants was performed using in silico predictive algorithms. RESULT: The targeted NGS research identified a total of 167 allelic variants of 22 genes in the study population; twenty-four patients had stable keratoconus (n. 54 variants) and forty patients had progressive disease (n. 113 variants). We identified genetic variants of certain pathogenic significance in five patients with progressive KC; in addition, eight novel genetic variants were found in eight patients with progressive KC. Mutations of FLG, LOXHD1, ZNF469, and DOCK9 genes were twice more frequently identified in patients with progressive than stable disease. Filaggrin gene variants were found in 49 patients (76% of total), of whom 32 patients (80% of progressive KC group) had progressive disease. CONCLUSIONS: Targeted NGS research provided new insights into the causative effect of candidate genes in the clinical phenotype of keratoconus. Filaggrin mutations were found to represent a genetic risk factor for development of progressive disease in Italy.

Ophthalmic Manifestations in Patients with Blood Malignancies.

Ocular complications can occur in up to 90% of patients with blood malignancies. Such complications range from direct infiltration to local hemostatic imbalance and treatment-related toxicity. This narrative review is based on a systematic computerized search of the literature conducted until January 2024 and examines the common ocular complications associated with blood cancers. Ocular complications from primary disease include mass effects from ocular adnexal lymphomas and intraocular lymphomas, with B-cell lymphomas accounting for 95% of primary ocular presentations. Secondary disease involvement from systemic hematological malignancies can lead to a wide range of ocular manifestations, such as leukemic retinopathy. Furthermore, toxicity from antineoplastic therapies and ocular graft versus host disease (oGVHD) after hematopoietic stem cell transplantation present additional risks to ocular health. In conclusion, ocular complications in blood cancer patients are an integral part of patient management, requiring regular ophthalmic evaluations and close collaboration between oncologists and ophthalmologists. Advances in therapy and an increased focus on early symptom recognition are essential for preserving vision and enhancing patient quality of life.

A Novel Ophthalmic Solution Containing Glicopro® Complex for the Treatment of Patients with Dry Eye Disease: Results from a Pilot Study.

(1) Background: Dry eye disease (DED) is a multifactorial ocular surface disease characterized by an imbalance in ocular surface homeostasis, and tear substitutes constitute the first line of treatment. The present study aimed to evaluate the changes in the signs and symptoms of patients with DED treated with a novel tear substitute containing the GlicoPro® complex. (2) Methods: Patients with DED not successfully responding to other tear substitutes were enrolled and treated with a novel ophthalmic solution (two drops four times daily). Patients were examined before starting the study treatment (T0) and after 30 (T1) and 60 (T2) days of treatment by means of Keratograph for the evaluation of the following: (i) tear meniscus height (TMH); (ii) noninvasive Keratograph break-up time (NIKBUT); (iii) bulbar redness; and (iv) infrared meibography. The SANDE questionnaire was administered to assess ocular discomfort symptoms. Analysis of the tear content of proenkephalin and Met/Leu-enkephalin was also performed. (3) Results: At T2, a significant improvement in NIKBUT first, average, and class, TMH, and SANDE score was found. The tear content of proenkephalins was significantly higher at T1, whereas processed active Met/Leu-enkephalins increased at both T1 and T2. (4) Conclusions: Our novel tear substitute based on GlicoPro® resulted in a significant improvement in ocular discomfort symptoms, tear volume, and stability in the patients treated. The increase in active peptides processed in tears may represent the pathophysiological substrate underlying this finding.

Noninvasive Ocular Surface Workup in Patients with Meibomian Gland Dysfunction Using Microwave-Heated Eye Bag.

Purpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag®) used serially for the treatment of meibomian gland dysfunction (MGD). Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2). Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded. Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability.

Longitudinal Changes of Cornea Volume Measured by Means of Anterior Segment-Optical Coherence Tomography in Patients with Stable and Progressive Keratoconus.

Keratoconus is a corneal disease which results in progressive thinning and protrusion of the cornea leading to irregular astigmatism. The purpose of this study was to evaluate longitudinal changes in corneal volume (CV) occurring over time in keratoconus eyes. Consecutive patients affected by keratoconus were evaluated by means of anterior segment-optical coherence tomography (AS-OCT) at two different time points: baseline (T0) and after 1 year (T1). Anterior and posterior refractive value; corneal thickness at the thinnest point (TP) and corneal volume (CV) calculated within discs of 3, 5 and 8 mm of diameter; anterior chamber depth (ACD); and anterior chamber volume (ACV) were obtained. Enrolled patients were divided into 3 groups (groups 1, 2, 3) according to the increasing disease severity and into 2 groups (groups A, B) according to the progression or stability of the disease. Overall, 116 eyes of 116 patients (76 males and 40 females, mean age 34.76 ± 13.99 years) were included. For the entire group of keratoconus patients, in comparison with T0, mean TP decreased at T1 from 458.7 ± 52.2 µm to 454.6 ± 51.6 µm (p = 0.0004); in parallel, mean value of CV calculated at 5 mm and 8 mm decreased significantly (from 10.78 ± 0.8 at T0 to 10.75 ± 0.79 at T1 (p = 0.02), and from 32.03 ± 2.01 mm3 at T0 to 31.95 ± 1.98 at T1 (p = 0.02), respectively). Conversely, there were no statistically significant differences in CV at 3 mm from T0 to T1 (p = 0.08), as well as for ACD and ACV. Regarding the course of the disease, patients belonging to group A showed statistically significant differences from T0 to T1 for TP, and for CV at 3 mm, 5 mm and 8 mm (p < 0.0001, p < 0.0001, p < 0.001 and p = 0.0058 respectively). There were no statistically significant differences for ACD (p = 0.6916) and ACV calculated at 3, 5 and 8 mm (p = 0.7709, p = 0.3765, p = 0.2475, respectively) in group A. At the same time, no statistically significant differences for ACD (p = 0.2897) and ACV calculated at 3, 5 and 8 mm (p = 0.9849, p = 0.6420, p = 0.8338, respectively) were found in group B. There were statistically significant positive correlations between changes of TP and CV at 3 mm (r = 0.6324, p < 0.0001), 5 mm (r = 0.7622, p < 0.0001) and 8 mm (r = 0.5987 p < 0.0001). In conclusion, given the strong correlation with TP, CV might be considered an additional AS-OCT parameter to be used in association with conventional parameters when detecting longitudinal changes in keratoconic eyes.

A Systematic Quality Assessment of Online Resources on Eyelid Ptosis Using the Modified Ensuring Quality Information for Patients (mEQIP) Tool.

BACKGROUND: Eyelid ptosis is an underestimated pathology deeply affecting patients' quality of life. Internet has increasingly become the major source of information regarding health care, and patients often browse on websites to acquire an initial knowledge on the subject. However, there is lack of data concerning the quality of available information focusing on the eyelid ptosis and its treatment. We systematically evaluated online information quality on eyelid ptosis by using the "Ensuring Quality Information for Patients" (EQIP) scale. MATERIALS AND METHODS: Google, Yahoo and Bing have been searched for the keywords "Eyelid ptosis," "Eyelid ptosis surgery" and "Blepharoptosis." The first 50 hits were included, evaluating the quality of information with the expanded EQIP tool. Websites in English and intended for general non-medical public use were included. Irrelevant documents, videos, pictures, blogs and articles with no access were excluded. RESULTS: Out of 138 eligible websites, 79 (57,7%) addressed more than 20 EQIP items, with an overall median score of 20,2. Only 2% discussed procedure complication rates. The majority fail to disclose severe complications and quantifying risks, fewer than 18% clarified the potential need for additional treatments. Surgical procedure details were lacking, and there was insufficient information about pre-/postoperative precautions for patients. Currently, online quality information has not improved since COVID-19 pandemic. CONCLUSIONS: This study highlights the urgent requirement for improved patient-oriented websites adhering to international standards for plastic and oculoplastic surgery. Healthcare providers should effectively guide their patients in finding trustworthy and reliable eyelid ptosis correction information. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Feasibility of Tear Meniscus Height Measurements Obtained with a Smartphone-Attachable Portable Device and Agreement of the Results with Standard Slit Lamp Examination.

PURPOSE: We aimed to evaluate the feasibility of using a novel device, the Smart Eye Camera (SEC), for assessing tear meniscus height (TMH) after fluorescein staining and the agreement of the results with measurements obtained using standard slit lamp examination. METHODS: TMH was assessed using both SEC and conventional slit lamp examination. The images were analyzed using the software ImageJ 1.53t (National Institutes of Health, Bethesda, MD, USA). A common measurement unit scale was established based on a paper strip, which was used as a calibration marker to convert pixels into metric scale. A color threshold was applied using uniform parameters for brightness, saturation, and hue. The images were then binarized to black and white to enhance the representation of the tear menisci. A 2 mm area around the upper and lower meniscus in the central eye lid zone was selected and magnified 3200 times to facilitate manual measurement. The values obtained using SEC were compared with those obtained with a slit lamp. RESULTS: The upper and lower TMH values measured using the SEC were not statistically different from those obtained with a slit lamp (0.209 ± 0.073 mm vs. 0.235 ± 0.085, p = 0.073, and 0.297 ± 0.168 vs. 0.260 ± 0.173, p = 0.275, respectively). The results of Bland-Altman analysis demonstrated strong agreement between the two instruments, with a mean bias of -0.016 mm (agreement limits: -0.117 to 0.145 mm) for upper TMH and 0.031 mm (agreement limits: -0.306 to 0.368 mm) for lower TMH. CONCLUSIONS: The SEC demonstrated sufficient validity and reliability for assessing TMH in healthy eyes in a clinical setting, demonstrating concordance with the conventional slit lamp examination.

Longitudinal Observation of Two Giant Peripheral Atrophic Retinal Holes Left Untreated.

In this report, two rare cases of large atrophic peripheral retinal holes are described. Both patients presented during a routine visit without reporting any ocular symptoms. The holes did not exhibit significant risk factors for progression to rhegmatogenous retinal detachment: No signs of posterior vitreous detachment, vitreoretinal tractions, or retinal degeneration were visible. For such asymptomatic cases, international guidelines recommend a strict follow-up schedule; however, the unusual size of the holes raised significant concerns about the management of these retinal breaks. The advantages and disadvantages of laser photo-coagulation treatment were discussed, ultimately favoring a watch-and-wait strategy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:176-178.].

Noninvasive screening of ocular surface disease in otherwise healthy patients scheduled for cataract surgery.

PURPOSE: To evaluate prevalence and characteristics of pathological ocular surface findings in healthy patients undergoing cataract surgery using a noninvasive ocular surface workup and a validated questionnaire. DESIGN: Prospective single-centre study (sub-analysis clinical trial no. NCT05754437). METHODS: Healthy patients undergoing senile cataract surgery were screened preoperatively by Oculus Keratograph (K5 M; Oculus GmbH, Wetzlar, Germany) for the evaluation of tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), and meibomian gland dropout. Ocular discomfort symptoms were scored by ocular surface disease index (OSDI) questionnaire. RESULTS: 120 eyes of 120 patients (62 females, 58 males; mean age 73.85 years, range 47-91 years) were included. All patients had at least 1 abnormal finding, while 19 (15.8%; 95% CI [0.09-0.22]) had alterations of all parameters. In detail, 39 patients (32.5%; 95% CI [0.24-0.41]) had pathological TMH (mean 0,15 mm [0.03 SD]), 102 (85%; 95% CI [0.79-0.91]) had pathological NIKBUT (mean 3.64 s [2.63 SD]), 117 (97.5%; 95% CI [0.95-1]) had some degree of gland dropout (mean 1.62 [0.70 SD]), 78 patients (65%; 95% CI [0.56-0.74]) had pathological OSDI scores (mean 28.63 [15.08 SD]). Using TFOS DEWS II criteria, 66 patients (55%; 95% CI [0.42-0.60]) resulted affected by dry eye. CONCLUSIONS: This quick noninvasive screening documented the high prevalence of pathological ocular surface parameters in patients without risk factors or previous diagnosis of dry eye who are scheduled for cataract surgery.

Effect of intralenticular dexamethasone implant: A case report.

INTRODUCTION: Intravitreal dexamethasone (DEX) implant is indicated for the treatment of macular oedema due to diabetic retinopathy, retinal vein occlusion and uveitis. The most common complications are cataract and elevated intraocular pressure (IOP). Accidental injection of DEX implant into the lens is a rare complication and only few papers presented it. CASE PRESENTATION: A 40-year-old man was treated with DEX implant for diabetic macular oedema in both eyes. At 1 week follow-up visit, slit lamp examination showed the DEX implant was located in the crystalline lens of the right eye (RE) without any sign of inflammation, cataract or elevated IOP, so we decided to plan a normal follow-up schedule. Macular oedema relapsed 5 months after the injection in the left eye (LE), whereas the RE did not show any sing of intraretinal or subretinal fluid. Six months after DEX implantation an uneventful phacoemulsification and intraocular lens placement were performed in the RE because of IOP elevation. CONCLUSIONS: The therapeutic effect of DEX implant can be maintained for a longer period of time than intravitreal implant, determining complete reabsorption of macular oedema. Intralenticular implant can be maintained inside the lens until either IOP increases, cataract progresses, or other complications occur.

Artificial intelligence in cornea and ocular surface diseases.

In modern ophthalmology, the advent of artificial intelligence (AI) is gradually showing promising results. The application of complex algorithms to machine and deep learning has the potential to improve the diagnosis of various corneal and ocular surface diseases, customize the treatment, and enhance patient outcomes. Moreover, the use of AI can ameliorate the efficiency of the health-care system by providing more accurate results, reducing the workload of ophthalmologists, allowing the analysis of a big amount of data, and reducing the time and resources required for manual image acquisition and analysis. In this article, we reviewed the most important and recently published applications of AI in the field of cornea and ocular surface diseases, with a particular focus on keratoconus, infectious keratitis, corneal transplants, and the use of in vivo confocal microscopy.

Anatomical and Functional Effects of an Oral Supplementation of Bromelain and Curcugreen in Patients with Focal Diabetic Macular Edema.

Diabetic retinopathy (DR) is one of the most severe diabetes-related complications, and macular edema stands as the primary contributor to the loss of central vision in individuals diagnosed with diabetes mellitus. The purpose of this study was to investigate the anatomical and functional effects of the oral administration of bromelain and curcugreen in patients controlled by therapy with non-proliferative DR presenting focal edema. Patients were enrolled and divided into two groups: group A (n = 18) received two tablets a day of bromelain and curcugreen (Retinil Forte®) orally, and group B (n = 15) underwent observation. The protocol included four visits: the screening visit (T0) and follow-up checks every 3 months up to 12 months (T3-T6-T9-T12). Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT) and vascular perfusion (VP) in superficial capillary plexus (SCP) and the deep capillary plexus (DCP) measured by optical coherence tomography angiography (OCTA) were analyzed. A mixed-design ANOVA was calculated to determine whether the change in BCVA, CMT, VP in SCP and DCP over time differed according to the consumption of Retinil Forte®. The results indicated that the interaction between time and treatment on the CMT and VP in DCP were significant, with F (4, 124) = 6.866 (p < 0.0001) and F (4, 124) = 3.263 (p = 0.0140), respectively. Conversely, the interaction between time and treatment was not significant on BCVA and VP in SCP with F (4, 124) = 1.121 (p = 0.3496) and F (4, 124) = 1.473 (p = 0.2146), respectively. In conclusion, our results suggest a protective role of the oral administration of bromelain and curcugreen in patients with DR and focal edema, in terms of the improvement of baseline CMT and VP in DCP over time.