Genotypic and phenotypic characterization of a cohort of patients affected by rod CNG channel-associated retinitis pigmentosa.

INTRODUCTION: Retinitis pigmentosa (RP), a heterogeneous inherited retinal disorder causing gradual vision loss, affects over 1 million people worldwide. Pathogenic variants in CNGA1 and CNGB1 genes, respectively accounting for 1% and 4% of cases, impact the cyclic nucleotide-gated channel in rod photoreceptor cells. The aim of this study is to describe and compare genotypic and clinical characteristics of a cohort of patients with CNGA1- or CNGB1-related RP and to explore potential genotype-phenotype correlations. METHODS: The following data from patients with CNGA1- or CNGB1-related RP, followed in five Italian inherited retinal degenerations services, were retrospectively collected: genetic variants in CNGA1 and CNGB1, best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, fundus photographs and short-wavelength fundus autofluorescence (SW-AF) images. Comparisons and correlation analyses were performed by first dividing the cohort in two groups according to the gene responsible for the disease (CNGA1 and CNGB1 groups). In parallel, the whole cohort of RP patients was divided into two other groups, according to the expected impact of the variants at protein level (Low and High group). RESULTS: In total, 29 patients were recruited, 11 with CNGA1- and 18 with CNGB1-related RP. In both CNGA1 and CNGB1, 5 novel variants in CNGA1 and 5 in CNGB1 were found. BCVA was comparable between CNGA1 and CNGB1 groups, as well as between Low and High groups. CNGA1 group had a larger mean EZ width compared to CNGB1 group, albeit not statistically significant, while EZ width did not differ between Low and High groups A statistically significant correlation between EZ width and BCVA as well as between EZ width and age were observed in the whole cohort of RP patients. Fundus photographs of all patients in the cohort showed classic RP pattern, and in SW-AF images an hyperautofluorescent ring was observed in 14/21 patients. CONCLUSION: Rod CNG channel-associated RP was demonstrated to be a slowly progressive disease in both CNGA1- and CNGB1-related forms, making it an ideal candidate for gene augmentation therapies.

Choroidal hypertransmission width on optical coherence tomography: a prognostic biomarker in idiopathic macular hole surgery.

PURPOSE: To test the hypothesis that optical coherence tomography (OCT) choroidal hypertransmission width (CHW) is a prognostic biomarker in idiopathic macular hole (MH) surgery METHODS: Retrospective cohort study of consecutive patients undergoing successful pars plana vitrectomy for idiopathic MH. We collected demographic, clinical, and OCT variables at the preoperative and last available visits. Two investigators assessed the following OCT parameters: MH minimum diameter, base diameter, CHW, ellipsoid zone, and external limiting membrane status (absent vs. present). Delta CHW was calculated as the difference between CHW and MH minimum diameter. Linear models were used to investigate factors associated with postoperative best-corrected visual acuity (BCVA) and BCVA change. RESULTS: Thirty-six eyes (36 patients) with a median (interquartile range (IQR)) follow-up of 9 (8-11) months were included. The median BCVA (IQR) improved from 0.75 (1-0.6) logMAR preoperatively to 0.2 (0.6-0.1) logMAR at the last visit (p < 0.001). Preoperative MH minimum diameter (for a 10-µm increase, estimate (standard error (SE)): 0.009 (0.003) logMAR, p = 0.003), base diameter (for a 10-µm increase, 0.003 (0.001) logMAR, p = 0.032), CHW (for a 10-µm increase, 0.008 (0.002) logMAR, p < 0.001), and delta CHW (for a 10-µm increase, 0.013 (0.005) logMAR, p = 0.009) were significantly associated with postoperative BCVA. The proportion of variance explained was the highest for MH CHW (R2 0.35), followed by minimum MH diameter (R2 0.24), delta CHW (R2 0.19), and MH base diameter (R2 0.14). None of the study variables was associated with delta BCVA. CONCLUSION: Preoperative CHW is associated with postoperative visual acuity in patients undergoing successful idiopathic MH surgery and may be a useful OCT prognostic biomarker.

Comparison Between 24-2 ZEST and 24-2 ZEST FAST Strategies in Glaucoma and Ocular Hypertension Using a Fundus Perimeter.

PRCIS: Using a Compass (CMP) (CMP, Centervue, Padova, Italy) fundus perimeter, Zippy Estimation by Sequential Testing (ZEST) FAST strategy showed a significant reduction in examination time compared with ZEST, with good agreement in the quantification of perimetric damage. PURPOSE: The aim of this study was to compare the test duration of ZEST strategy with ZEST FAST and to evaluate the test-retest variability of ZEST FAST strategy on patients with glaucoma and ocular hypertension. PATIENTS AND METHODS: This was a multicenter retrospective study. We analyzed 1 eye of 60 subjects: 30 glaucoma patients and 30 patients with ocular hypertension. For each eye we analyzed, 3 visual field examinations were performed with Compass 24-2 grid: 1 test performed with ZEST strategy and 2 tests performed with ZEST FAST. Mean examination time and mean sensitivity between the 2 strategies were computed. ZEST FAST test-retest variability was examined. RESULTS: In the ocular hypertension cohort, test time was 223±29 seconds with ZEST FAST and 362±48 seconds with ZEST (38% reduction, P <0.001). In glaucoma patients, it was respectively 265±62 and 386±78 seconds (31% reduction using ZEST FAST, P <0.001). The difference in mean sensitivity between the 2 strategies was -0.24±1.30 dB for ocular hypertension and -0.14±1.08 dB for glaucoma. The mean difference in mean sensitivity between the first and the second test with ZEST FAST strategy was 0.2±0.8 dB for patients with ocular hypertension and 0.24±0.96 dB for glaucoma patients. CONCLUSIONS: ZEST FAST thresholding provides similar results to ZEST with a significantly reduced examination time.

Effectiveness of a New Active Tear Substitute Containing 0.2% Hyaluronic Acid and 0.001% Hydrocortisone on Signs and Symptoms of Dry Eye Disease by Means of Low- and High-Tech Assessments.

INTRODUCTION: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog®, Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph®) assessments. METHODS: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score. RESULTS: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage. CONCLUSION: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3-6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests.

Sural Nerve Vertical Cross-Face Graft for Lacrimal Gland Neurotization to Improve Tear Secretion in Neurodeprivative Dry Eye.

PURPOSE: No specific interventions have been reported for the treatment of severe neurodeprivative dry eye disease owing to facial nerve palsy. We describe herein the feasibility of a novel surgical procedure to reinnervate the lacrimal gland and report the preliminary outcomes of the first series of patients who were treated accordingly. METHODS: Prospective interventional case series including consecutive patients affected by facial palsy with absolute deficiency of tear secretion who underwent lacrimal gland neurotization. A sural nerve vertical cross-face graft was used to connect the lacrimal gland with the parasympathetic branch of the lingual nerve directed to the contralateral submandibular gland. RESULTS: Lacrimal neurotization was performed uneventfully in 10 patients (4 M, 6 F; mean age 47.1 ± 17.1 years). In all cases, the procedure was combined with facial reanimation, while corneal neurotization was performed in 4 cases. One year postoperatively, mean values of a Schirmer test increased significantly compared with baseline values (7.56 ± 7.84 vs. 0 ± 0 mm/5 min; P = 0.02), while the mean daily number of instillation of tear substitutes decreased significantly (21.8 ± 4.5 vs. 7.1 ± 2.2; P = 0.009). Overall, all patients were satisfied with surgery (very satisfied: n = 7 and satisfied: n = 2). No major postoperative complications occurred. CONCLUSIONS: Vertical cross-face using a sural nerve graft to connect the lacrimal gland with the contralateral submandibular gland is a novel technique for treating patients with facial nerve palsy and severe neurodeprivative dry eye disease. This surgery both performed alone and combined with corneal neurotization is able to improve tear secretion and decrease the need for frequent instillations of tear substitutes.

Compass Fundus-Guided Perimetry in Geographic Atrophy.

Purpose: To evaluate compass (CMP), a recently introduced device that combines scanning ophthalmoscopy, automated perimetry, and eye tracking, for fundus-guided perimetry (microperimetry) with the purpose of correlating perimetric retinal sensitivity (PRS) and retinal geographic atrophy (GA) features. Materials and Methods: A retrospective, cross-sectional study was performed in 56 eyes of 43 patients affected by GA. All patients underwent compass 10-2 perimetry, consisting of a full-threshold visual field on fundus photography and an infrared (IR) image of the central 30° of the retina. Data were exported to an Excel sheet. Binarization with black/white (B/W) variables was applied on the compass photo fundus and matched with visual field scores. Patients underwent autofluorescence (AF) and IR images (Heidelberg, Germany): CMP and Heidelberg IR images were homologated by using GIMP software (https://www.gimp.org), and then atrophic areas were manually measured with the ImageJ program. CMP perimetric grid was overlapped with AF and IR pictures by using GIMP, obtaining composite TIFF images, which were then analyzed with the ImageJ greyscale score (GSS) tool. A hyperautofluorescent halo was identified on the GA edges of some patients. Pearson's correlation between GA size on IR compass and IR Heidelberg and between GSS and PRS values has been calculated; the independent t-test was realized to calculate the correlation between GSS and B/W variables identified on the CMP photo fundus. The Spearman correlation between total deviation and pattern deviation was calculated. Results: The AUC-ROC score between CMP scores and B/W variables was 93,4%. The Spearman correlation between total deviation and pattern deviation was highly significant (p = 0,00). The correlation between AF GSS values and PRS was significant (p value = 0,00), the correlation between GSS of hyperautofluorescent points and PRS was significant (p value = 0,00), and the correlation between IR GSS and PRS was significant (p value = 0,00). The correlation between AF GSS and B/W variables was significant (p value = 0,002), the correlation between hyperautofluorescent points and B/W was not significant (p value = 0,40), and the correlation between IR GSS and B/W was significant (p = 0,00). Conclusions: Based on our preliminary results, compass seems to be a reliable, quick, and safe device for the anatomical and functional study of GA. The direct visualization of the visual field on the fundus photography as a background allows a precise assessment and clinical monitoring of this disease.

Clinical Efficacy of an Eyedrop Containing Hyaluronic Acid and Ginkgo Biloba in the Management of Dry Eye Disease Induced by Cataract Surgery.

Purpose: To evaluate the prevalence of dry eye disease (DED) after cataract surgery, and the impact of hyaluronic acid and ginkgo biloba eyedrops (HA-GB). Methods: Forty patients with no DED received Ocular Surface Disease Index (OSDI) questionnaire, assessment of conjunctival hyperemia and epithelial damage, fluorescein tear break-up time (TBUT) at baseline, day 1, week 1, and 4; adherence and tolerability were checked at weeks 1 and 4. At day 0 patients underwent cataract surgery and were randomized to standard postoperative care (control group) or standard postoperative care + HA-GB 3 times a day for 4 weeks (HA-GB group). Results: At baseline, TBUT was 9.6 ± 2.6 sec in controls and 9.0 ± 1.6 in HA-GB; thereafter it was higher in HA-GB group: 5.8 ± 2.3 versus 7.8 ± 3.2 (week 1, P = 0.03) and 6.4 ± 2.3 versus 8.5 ± 2.5 (week 4, P = 0.009). OSDI and conjunctival hyperemia were better in HA-GB group at week 4; respectively, 9.0 ± 5.7 versus 14.8 ± 7.3 (P = 0.004) and 5% versus 35% (P = 0.04). In the last 2 visits 50% of controls were symptomatic (OSDI of 13 or higher) compared with 16% on HA-GB group (P < 0.001). In addition, tolerability was higher in HA-GB group (week 1: 0.81 ± 0.20 versus 0.70 ± 0.24, P = 0.007; week 4: 0.93 ± 0.17 versus 0.80 ± 0.28, P = 0.001). Conclusion: Treatment with HA-GB is effective in reducing DED signs and symptoms in patients receiving cataract surgery, with high tolerability and safety profiles. clinicaltrials.gov (ID number NCT05002036).

Inter-Eye Comparison of the Ocular Surface of Glaucoma Patients Receiving Surgical and Medical Treatments.

Background: Ocular surface frequently affects glaucoma patients. In this paper we aimed at evaluating the impact of glaucoma surgery on the ocular surface of patients who received unilateral trabeculectomy. Methods: 26 consecutive patients successfully treated with trabeculectomy on one eye (Trab Eye) and under control with topical treatments on the fellow eye (Med Eye) were included in this observational study. They received IDEEL and OSDI questionnaires, Tear Film Osmolarity (TFO), grading of conjunctival hyperemia, fluorescein tear break-up time (tBUT), grading of corneal staining and Schirmer test. Results: IDEEL and OSDI scores were 48 ± 38 and 11 ± 12, respectively, with moderate correlation (r = 0.50, p = 0.03). Compared with Med eyes, Trab Eyes had higher tBUT (6.5 ± 3.5 vs. 5.1 ± 2.7 s, p = 0.004), lower conjunctival hyperemia (0.8 ± 0.9 and 1.7 ± 1.1 respectively, p < 0.001) and lower corneal staining (0.3 ± 0.5 and 0.6 ± 0.5, respectively, p = 0.03). Correlation between corneal staining and conjunctival hyperemia was 0.55 in Trab Eyes (p = 0.01) and 0.44 in Med Eyes (p > 0.05). Patients with bilateral corneal staining had had threefold worse questionnaire scores (p < 0.05). The duration of treatment and the daily exposure to preservatives did not directly affect OS parameters in this cohort of patients. Conclusions: Patients receiving successful trabeculectomy showed better OS homeostasis (higher TBUT, lower grading of conjunctival hyperemia and corneal staining) than fellow medically treated eyes. Presence of corneal epithelial damage in both eyes is the factor more consistently affecting questionnaire scores.

Special Issue "Recommendations for Clinical Management of Glaucoma".

Glaucoma is a group of eye conditions that damage the optic nerve head and affect visual function, potentially leading to blindness [...].

Curcumin Supplementation (Meriva®) Modulates Inflammation, Lipid Peroxidation and Gut Microbiota Composition in Chronic Kidney Disease.

Chronic kidney disease (CKD) subjects suffer from high risk of cardiovascular mortality, and any intervention preventing the progression of CKD may have an enormous impact on public health. In the last decade, there has been growing awareness that the gut microbiota (GM) can play a pivotal role in controlling the pathogenesis of systemic inflammatory state and CKD progression. To ameliorate the quality of life in CKD subjects, the use of dietary supplements has increased over time. Among those, curcumin has demonstrated significant in vitro anti-inflammatory properties. In this pilot study, 24 CKD patients and 20 healthy volunteers were recruited. CKD patients followed nutritional counselling and were supplemented with curcumin (Meriva®) for six months. Different parameters were evaluated at baseline and after 3-6 months: uremic toxins, metagenomic of GM, and nutritional, inflammatory, and oxidative status. Curcumin significantly reduced plasma pro-inflammatory mediators (CCL-2, IFN-γ, and IL-4) and lipid peroxidation. Regarding GM, after 6 months of curcumin supplementation, Escherichia-Shigella was significantly lower, while Lachnoclostridium was significant higher. Notably, at family level, Lactobacillaceae spp. were found significantly higher in the last 3 months of supplementation. No adverse events were observed in the supplemented group, confirming the good safety profile of curcumin phytosome after long-term administration.

Spectral-Domain Optical Coherence Tomography Analysis in Syndromic and Nonsyndromic Forms of Retinitis Pigmentosa due to USH2A Genetic Variants.

INTRODUCTION: This study aimed to analyze macular structure by using spectral-domain optical coherence tomography (SD-OCT) in a cohort of patients affected by autosomal recessive retinitis pigmentosa and Usher syndrome, due to genetic variants in USH2A gene, and to correlate optical coherence tomography (OCT) parameters with functional and genetic data. METHODS: The subjects of this study were 92 patients, 46 syndromic (Usher syndrome type IIa [Ush2]) and 46 nonsyndromic (autosomal recessive RP [arRP]), with clinical and genetic diagnosis of USH2A-related retinal dystrophy, who underwent a complete ophthalmic examination and spectral-domain OCT analysis. The study focused on evaluating the differences between the 2 groups in the following parameters: best-corrected visual acuity (BCVA), ellipsoid zone (EZ) width, presence of epiretinal membrane (ERM), and cystic macular lesions (CMLs). Variants in USH2A gene were divided into 3 categories, according to the expected impact (low/high) at protein level of the different variants on each allele. RESULTS: BCVA and EZ width were significantly lower in Ush2 than in arRP patients (p < 0.0001 and p = 0.001). ERM was detected in 34.8% (16/46) of arRP patients and in 65.2% (30/46) of Ush2 patients (p = 0.003). CML was detected in 17.4% (8/46) of arRP patients and 30.4% (14/46) of Ush2 patients (p = 0.14). The allelic distribution was statistically different (p = 0.0003) by dividing the 2 diseases: for Ush2 patients it was 45.7% (high/high), 39.1% (low/high) and 15.2% (low/low); for arRP patients it was 8.7% (high/high), 56.5% (low/high), and 34.8% (low/low). The severity class of the variants significantly affected visual acuity and EZ width parameters (p = 0.004 and p = 0.002, respectively). CONCLUSION: Retinal disease, as evaluated by means of SD-OCT, shows more advanced degeneration signs in the syndromic than the nonsyndromic form of retinal dystrophy related to USH2A gene. Variant types and allelic profiles are determining factors for the onset of syndromic features. However, since the 3 allelic profiles can be found in both Usher and RP patients, other factors must necessarily play a determining role.

Comparison of Compass Suprathreshold Screening Strategies.

Screening programs may be useful to reduce the rate of undetected glaucoma. Compass (CMP, CenterVue, Padova, Italy) Standard Suprathreshold strategy (SST) analyses the visual function at 52 retinal locations. A new Quick Suprathreshold strategy (QST) reduces the number of tested locations to 24. With both tests, the CMP also provides an image of the central retina and a detail of the optic nerve head. The aim of this paper is to measure the performances of SST and QST compared with clinical diagnosis. 63 consecutive healthy subjects and 60 consecutive patients with perimetric defects from glaucoma in both eyes were recruited. They received one test per eye (SST or QST in randomized order); results were classified into normal, suspect and abnormal according to a global index provided in the report and called SupraThreshold Response (STR). Agreement between clinical diagnosis and test output were calculated, and test time was also measured. The agreement with the clinical diagnosis was 95.7% for SST and 95.1% for QST. When two suspect tests were excluded, agreement for QST increased to 96.7%. Test duration was 164 ± 82 s for SST and 71 ± 41 s for QST (p < 0.0001). Such a difference was similar in both glaucoma patients (respectively 231 ± 65 s vs. 105 ± 33 s, p < 0.0001) and normal subjects (98 ± 17 and 39 ± 9 s, p < 0.0001). In conclusion, SST and QST showed similar, high agreement with clinical judgement. Morphological analysis is potentially helpful in further improving the clinical usefulness of suprathreshold tests. QST is characterized by a strong time saving compared with SST.

Improving event-based progression analysis in glaucomatous visual fields.

Glaucoma is a progressive optic neuropathy with characteristic changes to the optic nerve head and the visual field (VF). Detecting progression of VF damage with Standard Automated Perimetry (SAP) is of paramount importance for clinical care. One common approach to detecting progression is to compare each new VF test to a baseline SAP test (event analysis). This comparison is made difficult by the test-retest variability of SAP, which increases with the level of VF damage, and the limited range of measurement, meaning that damage cannot be assessed below a certain level. We performed a prospective international multi-centre data collection of SAP data on 90 eyes from 90 people with glaucoma and different levels of VF damage over a short period of time (6 tests in 60 days). Data were collected using a fundus tracked perimeter (Compass, CenterVue). We used these data (minus the first test) to develop an improved event analysis that accounts for both the change in variability with damage and the lower bound on the measurement imposed by SAP. Using simulations, we show that our approach is more sensitive compared to previously developed methods, especially in the case of advanced glaucoma, while retaining similar specificity.

A Review of Topical and Systemic Vitamin Supplementation in Ocular Surface Diseases.

In the homeostasis of the ocular surface, vitamins play a critical role in regulating inflammatory responses and promoting cell differentiation, development and correct function. Systemic vitamin supplementation has been available for many decades; in recent years, thanks to pharmacological advancements, topical vitamin delivery has also become available in an attempt to better treat ocular surface disease (OSD) and dry eye disease (DED). In this paper, we reviewed the current evidence on the role of vitamin supplementation in OSD and DED. We originally searched the PubMed archive, inspected the references and restricted the search to pertinent papers. The body of evidence was evaluated using the amelioration of both signs and symptoms as the outcome, when available. We found that in patients with vitamin deficiency, systemic supplementation of Vitamin A is effective in treating OSD, reducing both DED signs and symptoms. Additionally, systemic supplementation of vitamin D is useful in reducing DED symptoms and increasing tear volume. Vitamin A is also effective in reducing DED signs and symptoms when administered locally. The efficacy of supplementation with other vitamins is still not fully proven. In conclusion, the inclusion of vitamins into the treatment strategies for OSD and DED allows for better treatment customization and better outcomes in these patients.

Microscope-Assisted Episcleral Surgery with Encircling Buckles and Chandelier Endoillumination for Primary Rhegmatogenous Retinal Detachment in Phakic and Pseudophakic Patients: A 12-Month Comparative Study.

INTRODUCTION: The aim of the study was to compare postoperative outcomes after microscope-assisted encircling buckle and chandelier endoillumination for primary rhegmatogenous retinal detachment (RRD) in phakic and pseudophakic (PFK) patients. METHODS: 121 eyes of 117 patients were divided into 2 groups depending on the lens status (group 1, PFK, 53 eyes; group 2, phakic, 68 eyes). The main outcomes include retinal reattachment rate (RRR) and best-corrected visual acuity (BCVA) at 1 week, 1, 3, 6, and 12 months. RESULTS: The overall primary RRR was 91.7% (111/121). In group 1, the primary RRR was 90.6% (48/53), whereas in group 2 it was 92.6% (63/68). The mean preoperative BCVA improved in both groups at 12 months. Undetected retinal breaks were found in 9.9% of cases. When an encircling 5-mm oval sponge was used, no additional exoplants were required and transcleral drainage was performed in 89.7% of the eyes. In group 1, among the 5 PFK eyes with persistent RRD, 4 eyes had a sulcus intraocular lens. CONCLUSIONS: Microscope-assisted episcleral surgery with chandelier endoillumination is an effective technique for primary RRD in both phakic and PFK eyes with uncomplicated cataract surgery. Chandelier endoilluminators help to visualize undetected retinal breaks, especially in PFK eyes. In case of a circumferential 5-mm oval sponge, additional exoplants are not required and transcleral drainage is strongly recommended to flatten the retina by closing the causative breaks.

Do Additional Testing Locations Improve the Detection of Macular Perimetric Defects in Glaucoma?

PURPOSE: To evaluate the ability of additional central testing locations to improve detection of macular visual field (VF) defects in glaucoma. DESIGN: Prospective cross-sectional study. PARTICIPANTS: Four hundred forty healthy people and 499 patients with glaucomatous optic neuropathy (GON) were tested with a fundus tracked perimeter (CMP; CenterVue) using a 24-2 grid with 12 additional macular locations (24-2+). METHODS: Glaucomatous optic neuropathy was identified based on expert evaluation of optic nerve head photographs and OCT scans, independently of the VF. We defined macular defects as locations with measurements outside the 5% and 2% normative limits on total deviation (TD) and pattern deviation (PD) maps within the VF central 10°. Classification was based on the total number of affected macular locations (overall detection) or the largest number of affected macular locations connected in a contiguous cluster (cluster detection). Criteria based on the number of locations and cluster size were used to obtain equivalent specificity between the 24-2 grid and the 24-2+ grids, calculated using false detections in the healthy cohort. Partial areas under the receiver operating characteristic curve (pAUCs) were also compared at specificities of 95% or more. MAIN OUTCOME MEASURES: Matched specificity comparison of the ability to detect glaucomatous macular defects between the 24-2 and 24-2+ grids. RESULTS: At matched specificity, cluster detection identified more macular defects with the 24-2+ grid compared with the 24-2 grid. For example, the mean increase in percentage of detection was 8% (95% confidence interval [CI], 5%-11%) and 10% (95% CI, 7%-13%) for 5% TD and PD maps, respectively, and 5% (95% CI, 2%-7%) and 6% (95% CI, 4%-8%) for the 2% TD and PD maps, respectively. Good agreement was found between the 2 grids. The improvement measured by pAUCs was also significant but generally small. The percentage of eyes with macular defects ranged from about 30% to 50%. Test time for the 24-2+ grid was longer (21% increase) for both cohorts. Between 74% and 98% of defects missed by the 24-2 grid had at least 1 location with sensitivity of < 20 dB. CONCLUSIONS: Visual field examinations with additional macular locations can improve the detection of macular defects in GON modestly without loss of specificity when appropriate criteria are selected.

Topical citicoline and vitamin B12 versus placebo in the treatment of diabetes-related corneal nerve damage: a randomized double-blind controlled trial.

BACKGROUND: To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy. METHODS: This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups. RESULTS: 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high. CONCLUSIONS: Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect. TRIAL REGISTRATION: Trial registration NCT03906513 , retrospectively registered on 08 April 2019.

Efficacy and Safety of VisuEvo® and Cationorm® for the Treatment of Evaporative and Non-Evaporative Dry Eye Disease: A Multicenter, Double-Blind, Cross-Over, Randomized Clinical Trial.

PURPOSE: To compare the efficacy of the new lubricating product VisuEvo® (VSE) vs Cationorm® (CTN) in patients with dry eye disease (DED). METHODS: Seventy-two patients with evaporative (n=54) and non-evaporative DED (n=18) were included in a multicenter, double-blind, 12-week cross-over study to receive VSE (6 weeks) and CTN (6 weeks) in randomized sequence. After baseline, two visits were performed during each period (intermediate and final visit, respectively at 2 and 6 weeks from the beginning of each period). Primary (tear break-up time, TBUT) and secondary endpoints (Schirmer I, Ferning, blink rate, osmometry, cytokine and lipid expression, ocular surface staining, patient satisfaction, and OSDI score) were compared. RESULTS: Sixty-three patients were evaluated for efficacy and 68 patients for safety. The intergroup differences for mean TBUT values were not significant at any study visit (baseline 3.2 ±1.5 sec; intermediate visits 4.5 ± 1.9 and 4.5 ± 1.8 sec in VSE and CTN groups, respectively, p = 0.10; final visits 5.4 ± 2.4 and 6.0 ± 3.1, respectively, p=0.63). Also, the assessment of secondary endpoints showed no significant difference between the two groups. The two study treatments were equally effective in evaporative and non-evaporative DED. The safety profile was excellent for both ocular treatments; transient blurred vision was observed in 11 patients only during CTN, 10 patients only during VSE, and 16 during both treatments. CONCLUSION: VSE was non-inferior to CTN in restoring tear film composition, increasing its stability and reducing ocular surface damage in evaporative and non-evaporative DED patients. STUDY IDENTIFIER: NCT03833882.