Evaluation of a new classification system for measuring the progression of ocular cystinosis: an analysis of 64 patients.

AIMS: To analyse the correlation between the physician categories defined by the 3C classification (crystal-complication-compliance) and the ocular manifestations of nephropathic cystinosis. METHODS: The last visit data of 64 patients aged between 2 and 64 attending the centre for management of cystinosis were reviewed. Each patient had been placed into one of four categories by the clinician based on disease severity. The correlation between these categories and markers of the disease was assessed using Pearson's correlation. RESULTS: Photophobia (0.647, p<0.001), visual acuity (-0.695, p<0.001), Gahl's score (0.603, p<0.001), optical coherence tomography (OCT)% (0.713, p<0.001) and in vivo confocal microscopy (IVCM)% (0.845, p<0.001), showed a strong, highly significant correlation between key signs and symptoms and the 3C classification. Corneal complications were strongly correlated with the 3C classification with scores of 0.802 (p<0.001), 0.634 (p<0.001), 0.726 (p<0.001) and 0.677 (p<0.001) for band keratopathy, keratitis, neovascularisation and corneal ulceration, respectively. 75% of those classified as most severe had all four complications. The use of artificial tears and ciclosporin strongly correlated with the categorisation, 0.574 (p<0.001) and 0.631 (p<0.001), respectively. With all cystinosis markers, the 3C classification showed a stronger correlation than age and crystal scores by Gahl's and OCT. Category and age were strongly correlated (0.656, p<0.001). There was a moderate negative correlation with therapeutic compliance with cysteamine eye-drops and categorisation (-0.422, p<0.001). The compliance pattern observed may help to explain why the disease progresses in some patients. CONCLUSION: 3C classification is a reliable tool to categorise ocular cystinosis and can support clinical management decisions allowing more reliable comparison of datasets.

Preservatives and ocular surface disease: A review.

Ocular surface disease (OSD) is a complex condition that can cause a range of symptoms (e.g, dryness, irritation, and pain) and can significantly impact the quality of life of affected individuals. Iatrogenic OSD, a common finding in patients with glaucoma who receive chronic therapy with topical ocular antihypertensive drugs containing preservatives such as benzalkonium chloride (BAK), has been linked to damage to the ocular surface barrier, corneal epithelial cells, nerves, conjunctival goblet cells, and trabecular meshwork. Chronic BAK exposure activates inflammatory pathways and worsens symptoms, compromising the success of subsequent filtration surgery in an exposure-dependent manner. In eyes being treated for glaucoma, symptomatic treatment of OSD may provide some relief, but addressing the root cause of the OSD often necessitates reducing or, ideally, eliminating BAK toxicity. Strategies to decrease BAK exposure in patients with glaucoma encompass the use of preservative-free formulations or drugs with alternative and less toxic preservatives such as SofZia®, Polyquad, potassium sorbate, or Purite®. Though the benefits of these alternative preservatives are largely unproven, they might be considered when financial constraints prevent the use of preservative-free versions. For patients receiving multiple topical preserved drugs, the best practice is to switch to nonpreserved equivalents wherever feasible, regardless of OSD severity. Furthermore, nonpharmacological approaches, including laser or incisional procedures, should be considered. This review explores the effects of BAK on the ocular surface and reviews strategies for minimizing or eliminating BAK exposure in patients with glaucoma in order to significantly improve their quality of life and prevent complications associated with chronic exposure to BAK.

Expert Consensus Recommendations for the Management of Ocular Surface Inflammation in Patients With Glaucoma.

PRCIS: We have developed through a consensus process 24 clinical recommendations for the comprehensive management of ocular surface inflammation in glaucoma patients, including diagnostic criteria, prevention measures, and treatment strategies according to ocular surface disease severity. PURPOSE: To obtain expert consensus on the diagnosis, prevention, and management of ocular surface inflammation (OSI) in patients with glaucoma. METHODS: An international steering committee of glaucoma and/or ocular surface disease (OSD) experts and a wider faculty of members from the Educational Club of Ocular Surface and Glaucoma (ECOS-G) collaborated to develop clinical recommendations on best practice in the management of OSI in glaucoma patients using a nonanonymous interactive quasi-Delphi process. Clinical recommendations were formulated by the steering committee based on an analysis of the recent literature to determine unmet needs, together with a web-based interactive survey of faculty members' opinion in seven identified areas of OSI management in glaucoma. Topics included (1) diagnosis of OSD, (2) diagnosis of OSI, (3) causes of OSI, (4) impact of OSD/OSI, (5) prevention of OSI, (6) treatment of OSI, and (7) inflammation and the deep structures of the eye. Faculty members were invited to vote on the clinical recommendations, and the steering committee then determined whether consensus had been achieved. RESULTS: Consensus was obtained on 24 clinical recommendations by 80%-100% of faculty members. There was consensus that OSI should be investigated in all glaucoma patients. The main prevention measure in glaucoma patients with pre-existing OSD was the elimination/minimisation of preserved medications, especially BAK-preserved eye drops. A subtractive treatment strategy rather than an additive strategy is recommended according to OSI/OSD severity to improve the ocular health and/or before glaucoma surgery. CONCLUSION: These recommendations for the management of OSI in glaucoma should be useful to guide decision-making in clinical practice.

The PRAMOS Study: PRostaglandin Analogues Monotherapy-Awareness Survey on Ocular Surface Involvement.

INTRODUCTION: Even though the local tolerance of prostaglandin (PG) analogues has improved drastically since the introduction of preservative-free (PF) eye drops, prescription patterns still vary widely among practitioners and between countries and could have an impact on the ocular surface of treated patients and, in consequence, their adherence. The aim of this study is to explore the prescribing patterns of PG analogues monotherapy in France and to evaluate their impact on ocular surface status. METHODS: This was a national multicenter cross-sectional observational study that was conducted by 18 glaucoma experts in France. Patients over 18 years of age and receiving monotherapy with topical PG analogues for the treatment of ocular hypertension and/or glaucoma, with no history of prior glaucoma surgery, were consecutively selected from the glaucoma outpatient clinics of participating physicians and underwent an ocular surface examination. RESULTS: A total of 344 eyes of 344 patients were enrolled between November 2022 and November 2023. Prescribed PG monotherapy was PF in 271 (78.7%) patients. Clinical history and ocular surface evaluation indicated that 79.4% of the study population (n = 273) presented with at least one symptom or clinical sign of dry eye and that three patients out of four had an unstable tear film. Subgroup analysis comparing preserved and PF PG analogues showed a higher prevalence of conjunctival hyperemia and corneal staining in the preserved group. Multivariate analysis identified conjunctival hyperemia as consistently associated with preservative use (odds ratio = 7.654; p = 0.003 for moderate conjunctival hyperemia). CONCLUSIONS: This study highlights the growing trend toward PF PG analogue prescriptions by specialists in France. However, ocular surface issues remain prevalent, impacting patient adherence and treatment efficacy. Comprehensive ocular surface examinations are crucial in glaucoma management to enhance long-term tolerance, compliance, and overall treatment success.

Review of clinical outcomes of a cationic emulsion tear substitute in patients with dry eye disease.

First-line options for the treatment of dry eye disease (DED) rely on artificial tears (ATs), among which cationic emulsion (CE)-based ATs have been developed in order to mimic the healthy tear film for an improved restoration of the ocular surface homeostasis. In this review, we describe the outcomes reported in several studies, assessing the mode of action, ocular tolerance and clinical performance of a CE-based AT. Pilot studies have revealed that CE-based ATs can increase the volume and stability of the tear film while limiting its evaporation rate. Larger studies have demonstrated that CE-based ATs play a significant role in the improvement of both objective and subjective DED parameters, including superior efficacy on DED symptoms compared to several other available AT formulation types. Concomitantly, CE-based ATs have been shown to help patients to prevent or recover from corneal defects associated with refractive surgery. These positive outcomes on ocular surface epithelia are likely due to the combination of unique rheological behaviour and intrinsic anti-inflammatory properties. Based on all clinical findings, CE-based ATs represent a valuable treatment option for patients with various etiologies of DED including evaporative forms and would deserve evaluation of benefits in other surgical intervention types triggering DED.

Short-Term Efficacy and Safety of Phacoemulsification Associated With iStent Inject W in Patients With Controlled Open Angle Glaucoma.

PRCIS: The iStent inject W implanted during phacoemulsification effectively reduces IOP. PURPOSE: The purpose of this study was to evaluate the efficacy and safety of iStent inject W combined with phacoemulsification in patients with controlled open angle glaucoma undergoing cataract surgery. PATIENTS AND METHODS: We conducted a retrospective, bicentric study of patients with controlled chronic open angle glaucoma who underwent phacoemulsification combined with the injection of 2 iStent inject Ws. Patient characteristics, including intraocular pressure (IOP) and the number of glaucoma medications, were evaluated preoperatively and 1 week, 1 month, and 6 months postoperatively. The primary end point was IOP reduction, and the secondary end point was the reduction in the number of glaucoma medications. RESULTS: In this study, 85 eyes were included. The majority of patients had primary open angle glaucoma (85% of eyes). Preoperative mean IOP was 16.1±2.0 mm Hg with a mean of 2.3±0.5 glaucoma medications. At 1 week postoperatively, the mean IOP was 16.7±3.1 mm Hg with a mean of 2.0±0.7 hypotensive medications. At 1 and 6 months, the mean IOP was 14.2±2.1 and 13.0±1.5 mm Hg, with a mean of 2.0±0.6 and 1.8±0.5 glaucoma medications, respectively. The percentage IOP reduction at 1 and 6 months was 11.6% ( P =0.001) and 19.3% ( P <0.0001), respectively. Regarding glaucoma medications, at 1 and 6 months, the reduction in the number of medications was 12.9% ( P =0.025) and 22.4% ( P =0.003), respectively. The most frequent significant postoperative adverse events were corneal edema in 7%, IOP spikes in 6%, and hyphema in 6% of eyes, which resolved spontaneously. CONCLUSIONS: The iStent inject W implanted during phacoemulsification effectively reduces IOP and the number of glaucoma medications needed at 6 months of follow-up, with a favorable safety profile in patients with controlled open angle glaucoma.

TFOS Lifestyle: Impact of elective medications and procedures on the ocular surface.

The word "elective" refers to medications and procedures undertaken by choice or with a lower grade of prioritization. Patients usually use elective medications or undergo elective procedures to treat pathologic conditions or for cosmetic enhancement, impacting their lifestyle positively and, thus, improving their quality of life. However, those interventions can affect the homeostasis of the tear film and ocular surface. Consequently, they generate signs and symptoms that could impair the patient's quality of life. This report describes the impact of elective topical and systemic medications and procedures on the ocular surface and the underlying mechanisms. Moreover, elective procedures performed for ocular diseases, cosmetic enhancement, and non-ophthalmic interventions, such as radiotherapy and bariatric surgery, are discussed. The report also evaluates significant anatomical and biological consequences of non-urgent interventions to the ocular surface, such as neuropathic and neurotrophic keratopathies. Besides that, it provides an overview of the prophylaxis and management of pathological conditions resulting from the studied interventions and suggests areas for future research. The report also contains a systematic review investigating the quality of life among people who have undergone small incision lenticule extraction (SMILE). Overall, SMILE refractive surgery seems to cause more vision disturbances than LASIK in the first month post-surgery, but less dry eye symptoms in long-term follow up.

Management of inflammation in dry eye disease: Recommendations from a European panel of experts.

INTRODUCTION: Early initiation of anti-inflammatory therapies is recommended for dry eye disease (DED) to break the vicious cycle of pathophysiology. However, there is limited guidance on how to implement topical ciclosporin (CsA) and corticosteroid treatment into clinical practice. This expert-led consensus provides practical guidance on the management of DED, including when and how to use topical CsA. METHODS: A steering committee (SC) of seven European DED experts developed a questionnaire to gain information on the unmet needs and management of DED in clinical practice. Consensus statements on four key areas (disease severity and progression; patient management; efficacy, safety and tolerability of CsA; and patient education) were generated based on the responses. The SC and an expanded expert panel of 22 members used a nine-point scale (1 = strongly disagree; 9 = strongly agree) to rate statements; a consensus was reached if ≥75% of experts scored a statement ≥7. RESULTS: A stepwise approach to DED management is required in patients presenting with moderate corneal staining. Early topical CsA initiation, alone or with corticosteroids, should be considered in patients with clinical risk factors for severe DED. Patient education is required before and during treatment to manage expectations regarding efficacy and tolerability in order to optimise adherence. Follow-up visits are required, ideally at Month 1 and every 3 months thereafter. Topical CsA may be continued indefinitely, especially when surgery is required. CONCLUSION: This consensus fills some of the knowledge gaps in previous recommendations regarding the use of topical corticosteroids and CsA in patients with DED.

Safety and Efficacy of the Preserflo® Microshunt in Refractory Glaucoma: A One-Year Study.

Purpose: To evaluate the safety and efficacy of Preserflo® microshunt implantation in eyes with refractory glaucoma. Methods: In this retrospective study, a cohort of patients who underwent Preserflo® microshunt implantation between April 2019 and August 2020 for refractory glaucoma were evaluated. At the time of surgery, all eyes had uncontrolled intraocular pressure (IOP) despite maximally tolerated medical therapy and at least one previous failed glaucoma filtering surgery. The primary outcome was a complete success, defined as postoperative IOP ≤ 21 mm Hg with an IOP reduction ≥ 20% and no repeat filtering surgery. The secondary outcome was qualified success, defined as a complete success with the use of antiglaucoma medications. The rates of needling, bleb repair, and postoperative complications were also recorded. Results: Forty-seven eyes with a mean preoperative IOP of 30.1 ± 7.1 mm Hg and a mean of 3.4 ± 1 glaucoma medications were included. The mean number of previous surgeries prior to microshunt implantation was 2.3 ± 1.3. After 1 year, the mean IOP was significantly reduced to 18.8 ± 4.6 mm Hg, with the mean number of medications significantly reduced to 1.4 ± 1.2. Complete success was achieved in 35% of eyes, and a qualified success in 60% of eyes. A decrease in IOP of at least 30% was found in 55% of eyes. Needling or bleb repair was performed in 49% of eyes. Complications were minimal and transient, except for one eye which presented with tube extrusion, and another eye with a transected tube. A repeat glaucoma surgery had to be performed in 17% of eyes. Conclusions: The Preserflo® Microshunt provided moderate success but a significant reduction in IOP, with a good safety profile after one year of follow-up in eyes at high risk for failure of filtering surgery.

In vivo confocal microscopic study of corneal innervation in Sjögren's Syndrome with or without small fiber neuropathy.

PURPOSE: To study changes in the subbasal nerve plexus by In vivo confocal microscopy (IVCM) in Sjögren's Syndrome (SS) with or without associated Small Fiber Neuropathy (SFN), in order to prevent diagnostic delay. METHODS: Seventy-one patients with SS, including 19 with associated SFN, 20 healthy volunteers and 20 patients with Meibomian gland dysfunction (MGD) were included in this retrospective case-control study. IVCM was used to investigate subbasal nerve plexus density and morphology. RESULTS: Corneal sensitivity as evaluated with the Cochet-Bonnet aesthesiometer was significantly reduced in the SS group versus the control group (P = 0.026) and the MGD group (P = 0.037). The number of inflammatory cells was significantly increased in the SS group to 86.2 ± 82.1 cells/mm2 compared to the control group (P < 0.001). The density of the subbasal nerve plexus was significantly reduced to 16.7 ± 6.5 mm/mm2 in the SS group compared to the control group (P < 0.005) and the MGD group (P = 0.042). The tortuosity of the nerves in the SS group was significantly increased compared to the control group (P < 0.001) and the MGD group (P = 0.025). The average number of subbasal nerve plexus neuromas was significantly increased in the SS group compared to the control group (P = 0.001), with a significant increase in the average number of neuromas in SS patients with associated SFN compared to SS patients without SFN (P = 0.008). CONCLUSION: IVCM can be useful to detect corneal nerve changes in SS patients and may allow earlier diagnosis of the disease and to consider new therapeutic approaches.

Evaluation of neuroprotective and immunomodulatory properties of mesenchymal stem cells in an ex vivo retinal explant model.

BACKGROUND: Glaucoma is a blinding degenerative neuropathy in which the death of retinal ganglion cells (RGCs) causes progressive loss of visual field and eventually vision. Neuroinflammation appears to be a key event in the progression and spread of this disease. Thus, microglial immunomodulation represents a promising therapeutic approach in which mesenchymal stem cells (MSCs) might play a crucial role. Their neuroprotective and regenerative potentials have already raised hope in animal models. Yet no definitive treatment has been developed, and some safety concerns have been reported in human trials. In the present study, we investigated the neuroprotective and immunomodulatory properties as well as the safety of MSCs in an ex vivo neuroretina explant model. METHODS: Labeled rat bone marrow MSCs were placed in coculture with rat retinal explants after optic nerve axotomy. We analyzed the neuroprotective effect of MSCs on RGC survival by immunofluorescence using RBPMS, Brn3a, and NeuN markers. Gliosis and retinal microglial activation were measured by using GFAP, CD68, and ITGAM mRNA quantification and GFAP, CD68, and Iba1 immunofluorescence stainings. We also analyzed the mRNA expression of both 'M1' or classically activated state inflammatory cytokines (TNFα, IL1ß, and IL6), and 'M2' or alternatively activated state microglial markers (Arginase 1, IL10, CD163, and TNFAIP6). RESULTS: The number of RGCs was significantly higher in retinal explants cultured with MSCs compared to the control group at Day 7 following the optic nerve axotomy. Retinal explants cultured with MSCs showed a decrease in mRNA markers of gliosis and microglial activations, and immunostainings revealed that GFAP, Iba1, and CD68 were limited to the inner layers of the retina compared to controls in which microglial activation was observed throughout the retina. In addition, MSCs inhibited the M1 phenotype of the microglia. However, edema of the explants was observed in presence of MSCs, with an increase in fibronectin labeling at the surface of the explant corresponding to an epiretinal membrane-like phenotype. CONCLUSION: Using an ex vivo neuroretina model, we demonstrated a neuroprotective and immunomodulatory effect of MSCs on RGCs. Unfortunately, the presence of MSCs also led to explant edema and epiretinal membrane formation, as described in human trials. Using the MSC secretome might offer the beneficial effects of MSCs without their potential adverse effects, through paracrine signaling.

Anterior chamber fibrin reaction during Descemet membrane endothelial keratoplasty.

PURPOSE: To report a series of five cases of intraoperative spontaneous anterior chamber fibrin reaction during Descemet Membrane Endothelial Keratoplasty (DMEK). METHODS: We retrospectively collected demographic data and data for ocular disease history for each patient. Donor age, preoperative graft endothelial density, surgical complications on surgery and intraoperative OCT videos, intraoperative management and outcome were assessed. The same standardized DMEK technique was used for all patients. RESULTS: We report intraoperative fibrin formation in five eyes subjected to DMEK. Three pseudophakic eyes underwent single DMEK, and the other two underwent combined DMEK and cataract surgery. In one case, a fibrin filament was observed before graft insertion, with multiplication during surgery, whereas, in the other four cases, strands of fibrin from the iris appeared after graft insertion. This complication resulted in graft failure in four cases (80%). No recipient- or donor-related risk factor was identified. CONCLUSIONS AND IMPORTANCE: The anterior chamber fibrin reaction is a very uncommon complication of DMEK. The underlying pathophysiological mechanisms remain unknown, but analyses of surgical videos and intraoperative OCT suggest iris involvement. This phenomenon may be induced by chronic subclinical anterior chamber inflammation, due to a blood-aqueous barrier breakdown associated with acute iris trauma during surgery. Thus, intraoperative microtraumatism of the iris should be avoided.

Anterior chamber tap cytology in acute postoperative endophthalmitis: a case-control study.

AIMS: To determine anterior chamber tap cytology characteristics in acute postoperative bacterial endophthalmitis. METHODS: 488 eyes of 488 patients were included in this retrospective case-control study. The study group included 93 eyes with bacteriologically documented endophthalmitis and 85 eyes with clinical endophthalmitis. The control group included 33 eyes with non-infectious postoperative inflammation, 116 eyes with acute uveitis and 161 cataract surgery eyes with no ocular inflammation. Cytological analysis, direct examination and microbiological cultures were performed in aqueous humour (AqH) samples. Inclusion criteria for the study group were the following: suspected endophthalmitis within 30 days following cataract surgery by phacoemulsification, secondary lens implantation, pars plana vitrectomy or intravitreal injection; best-corrected visual acuity (BCVA) <20/400; hypopyon or cyclitic membrane; absence of visibility of the retina; vitritis at a slit-lamp examination or in ultrasound B-scan. RESULTS: Cell line counts (mainly polymorphonuclear neutrophils) were significantly higher in the two endophthalmitis study subgroups than in the three control subgroups. The study group showed a predominance of polymorphonuclear neutrophils as opposed to the three control subgroups including uveitis (p<0.00001). The best sensitivity/specificity was obtained using a polymorphonuclear neutrophil threshold of 10 per field (sensitivity, 0.90; specificity, 0.75). The sensitivity of the bacterial culture was 32% in the AqH. High neutrophil count was associated with poorer initial BCVA (rs=0.62; p<0.00001) and higher risk of retinal detachment during (p=0.04) and after (p<0.001) hospitalisation. CONCLUSION: Anterior chamber tap cytology is a quick and accessible tool complementary to culture and PCR for the management of acute postoperative endophthalmitis.

Corneal Nerve Abnormalities in Painful Dry Eye Disease Patients.

Background: This study aimed to compare the corneal nerve structural abnormalities detected using in vivo confocal microscopy (IVCM) in patients with neuropathic corneal pain (NCP) secondary to primary meibomian gland dysfunction (MGD) or autoimmune dry eye (AIDE). Methods: A two-stage retrospective nested case-control study was conducted. First, data from patients with either MGD or AIDE were assessed, selecting only cases with no corneal pain (VAS = 0) or severe pain (VAS ≥ 8). Ocular signs and symptoms of the 238 selected patients were compared between painful and painless cases. Next, painful patients with no corneal damage (Oxford score ≤ 1) were selected within each study group, defining the cases with NCP (i.e., "pain without stain"). IVCM images from all groups were compared with prospectively-recruited healthy controls, focusing on dendritiform cell density and nerve abnormalities (density, tortuosity, microneuromas). Results: AIDE patients had more ocular signs/symptoms than MGD patients. Compared with healthy controls, AIDE-related NCP patients showed increased nerve tortuosity and number of neuromas, whereas MGD-related NCP patients had reduced nerve density and increased number, perimeter, and area of microneuromas. Microneuromas were also observed in healthy controls. Furthermore, a higher number of microneuromas was found in MGD-related NCP compared to AIDE-related NCP or painless MGD. Conclusions: MGD-related NCP was associated with significantly more corneal nerve abnormalities than AIDE-related NCP or healthy controls. Although IVCM can be useful to detect NCP-related corneal nerve changes in such patients, the diagnosis of dry eye disease-related NCP will require an association of several IVCM-based criteria without relying solely on the presence of microneuromas.

Corneal Changes in Acanthamoeba Keratitis at Various Levels of Severity: An In Vivo Confocal Microscopic Study.

Purpose: To investigate the relationship between Acanthamoeba cysts and inflammatory cells in Acanthamoeba keratitis (AK) by in vivo confocal microscopy (IVCM). Methods: A case-control study included 30 patients with AK and 20 normal controls. The severity of the AK was divided into mild, moderate, and severe. The central cornea and four standard quadrants of the peripheral cornea were imaged by IVCM. The cyst infiltration and dendritic cell (DC) density and maturity (size, length, field, and number of dendrites) were quantified. The relationship between clinical severity, cyst density, and DC alterations was characterized by Spearman correlation analysis. Results: The maximum cyst density in the mild, moderate, and severe groups was 31.3 cysts/mm2 (17.2-32.8), 62.5 cysts/mm2 (59.3-103.1), and 162.5 cysts/mm2 (65.6-215.6), respectively. Compared to normal participants, a significant increase in the mean corneal DC density was detected in patients with AK (290.2 ± 97.0 vs. 25.3 ± 8.3 cells/mm2; P < 0.001). Patients with AK presented an increase in median DC size (178.3 vs. 63.6 µm2/cell, P < 0.001), median DC field (518.1 vs. 256.6 µm2/cell, P = 0.008), and median DC dendrite length (42.3 vs. 14.7 µm/cell, P < 0.001). Increased AK severity was correlated with an increase in cyst density, DC size, and dendrite length (all P < 0.05). An increase in cyst density was significantly correlated with an increase in DC density (ß = 0.484, P = 0.026) and DC size (ß = 0.557, P = 0.009). Conclusions: Cyst density and depth of infiltration as well as maturity of the surrounding DC increased significantly with the severity of AK. Translational Relevance: Quantitative analysis of cyst density and DC maturity may provide a new method of evaluating the severity of AK.

Capsazepine decreases corneal pain syndrome in severe dry eye disease.

BACKGROUND: Dry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED. METHODS: Chronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests. RESULTS: First, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED. CONCLUSION: These data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.

Inflammation in Glaucoma: From the back to the front of the eye, and beyond.

The pathophysiology of glaucoma is complex, multifactorial and not completely understood. Elevated intraocular pressure (IOP) and/or impaired retinal blood flow may cause initial optic nerve damage. In addition, age-related oxidative stress in the retina concurrently with chronic mechanical and vascular stress is crucial for the initiation of retinal neurodegeneration. Oxidative stress is closely related to cell senescence, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, which are involved in glaucoma progression. Accumulating evidence from animal glaucoma models and from human ocular samples suggests a dysfunction of the para-inflammation in the retinal ganglion cell layer and the optic nerve head. Moreover, quite similar mechanisms in the anterior chamber could explain the trabecular meshwork dysfunction and the elevated IOP in primary open-angle glaucoma. On the other hand, ocular surface disease due to topical interventions is the most prominent and visible consequence of inflammation in glaucoma, with a negative impact on filtering surgery failure, topical treatment efficacy, and possibly on inflammation in the anterior segment. Consequently, glaucoma appears as an outstanding eye disease where inflammatory changes may be present to various extents and consequences along the eye structure, from the ocular surface to the posterior segment, and the visual pathway. Here we reviewed the inflammatory processes in all ocular structures in glaucoma from the back to the front of the eye and beyond. Our approach was to explain how para-inflammation is necessary to maintain homoeostasis, and to describe abnormal inflammatory findings observed in glaucomatous patients or in animal glaucoma models, supporting the hypothesis of a dysregulation of the inflammatory balance toward a pro-inflammatory phenotype. Possible anti-inflammatory therapeutic approaches in glaucoma are also discussed.

Long-term follow-up of cystinosis patients treated with 0.55% cysteamine hydrochloride.

BACKGROUND/AIMS: Cystinosis is a rare, autosomal recessive disorder causing defective transport of cystine out of lysosomes. Cystadrops (0.55% cysteamine hydrochloride in viscous solution) has been used on a named-patient basis to treat the accumulation of cystine crystals in the cornea in patients with cystinosis. METHODS: Retrospective analysis of the Temporary Authorisation for Use cohort of 130 patients who received Cystadrops between 2013 and 2017 in France. RESULTS: Patients received an average dosage of 3.3 (±0.94) instillations per eye per day. Over the duration of follow-up, of up to 45 months, patients maintained visual acuity scores of 0.0, which approximated normal. Corneal cystine crystal scores tended to decrease over time, stabilising after around 27 months between 1.22 and 1.87. Photophobia decreased within 3 months, stabilising on scores of around 1.5 and 1.7. 47 non-serious adverse reactions were reported, which were generally transient irritation, stinging or blurred vision. Four serious adverse events were reported, including keratitis and corneal ulcer, but these may have been caused by the underlying disease. CONCLUSION: This large safety cohort confirms the efficacy, safety and tolerability of Cystadrops in real-world clinical practice.

Micropulse transscleral cyclophotocoagulation using a standard protocol in patients with refractory glaucoma naive of cyclodestruction.

PURPOSE: To assess the efficacy and safety of a standardized micropulse transscleral diode laser cyclophotocoagulation procedure in refractory glaucoma. METHODS: Retrospective, interventional study in a series of 37 consecutive patients with refractory glaucoma, cyclodestructive procedure-naive, who underwent micropulse transscleral diode laser cyclophotocoagulation from December 2016 to October 2017. A successful laser treatment was defined as (1) intraocular pressure between 6 and 18 mm Hg; (2) 20% of baseline intraocular pressure reduction; (3) no additional glaucoma medications; (4) no decrease in vision due to complications or change in intraocular pressure; and (5) no need for additional glaucoma surgery except micropulse transscleral diode laser cyclophotocoagulation retreatment. RESULTS: Mean age was 60.2 years. Mean follow-up was 9.7 ± 3.9 months. The mean preoperative intraocular pressure (28.7 mm Hg) significantly decreased to 21.0 mm Hg at 1 month, 18.5 mm Hg at 3 months, 18.4 mm Hg at 6 months, and 18.5 mm Hg at 12 months (p < 0.01 at all time points). The mean number of preoperative glaucoma medications (4.7) decreased to 4.0 at 1 month (p = 0.14), 4.5 at 3 months (p < 0.05), 3.9 at 6 months (p < 0.05), and 3.6 at 12 months (p < 0.05). At 1 year, the success rate was 35% with a mean intraocular pressure lowering of 36%. One patient had hypotony and a loss of best-corrected visual acuity. Mild transient postoperative inflammation was observed in 8% of the cases. CONCLUSION: Using a standardized procedure, micropulse transscleral diode laser cyclophotocoagulation allows a mild intraocular pressure decrease with a low rate of complications and thus achieves a relatively good profit risk benefit, mostly for moderately hypertensive refractory glaucoma.

Ocular surface assessment in times of sanitary crisis: What lessons and solutions for the present and the future?

PURPOSE: To describe the immediate consequences of SARS-CoV-2 and the COVID-19 pandemic on the ocular surface and eye-care professionals, and to discuss the need for a mandatory switch from currently performed tele-screening to true teleconsultation for remote ocular surface assessment. MAIN FINDINGS: Ophthalmologists have been largely impacted by the COVID-19 sanitary crisis, due to both the ocular manifestations of SARS-CoV-2 and to the high contagiousness of the virus. The proximity of ophthalmologists to their patients have pushed eye-care providers to readapt their practices and develop alternatives to face-to-face consultations. However, teleconsultation has some major limitations and drawbacks, especially for ocular surface assessment that relies on high-quality graphic data for adequate diagnosis. Tele-screening, on the other hand, emphasizes on the importance of history-taking and listening to the patient in order to adequately prioritize appointments based on the presumed degree of emergency. CONCLUSION: Despite all the enthusiasm, tele-screening as currently performed with the available tools is still not capable of completely replacing a standard ophthalmic examination for the assessment of ocular surface diseases. While waiting for new emerging technologies and future implementation of imaging modalities and artificial intelligence, decision making algorithms can help eye-practitioners remotely screen their patients to assess the optimal time for follow-up appointments.