Prophylactic Therapy for Long-Term Ocular Discomfort After Cataract Surgery.

PURPOSE: The cataract surgery dissatisfaction rate is 20% to 35% due to ocular surface discomfort. We investigate the ocular surface discomfort after surgical failure as a consequence of age-related parainflammation. We also aim to prevent it by immune-modulating prophylactic management. METHODS: Monocentric clinical trial realized in a teaching hospital. Prospective, randomized, open-label, unmasked clinical trial. One hundred patients diagnosed with cataracts underwent phacoemulsification surgery. Groups A (<65 years; n = 25) and B (>75 years; n = 25) received surgery only. Groups C and D (both >75 years and both n = 25) used cyclosporine A 0.1% cationic emulsion (CE) eye drops or CE lubricating eye drops (both twice daily), respectively, for 30 days before surgery. Patients were followed up 90 days after surgery. The primary outcome was postoperative ocular surface failure; secondary outcomes examined the influence of prophylactic cyclosporine A 0.1% CE therapy on ocular surface outcomes. RESULTS: Group B demonstrated greater severity regarding ocular surface signs and symptoms throughout the study period, versus all other groups. Signs/symptoms were typically lower in Group A. Group C achieved significant reductions in conjunctival Symptom Assessment in Dry Eye values ( P < 0.05), conjunctival hyperemia severity ( P < 0.01), and meibomian gland dysfunction ( P < 0.001) at Day 45, versus Group B, and tear break-up time was increased ( P < 0.001). Ocular surface inflammatory marker transcription (HLADR, intercellular adhesion molecule 1 [ICAM-1], and interleukin 6 [IL-6]) was significantly downregulated in Group C, versus Group B, at 90 days ( P < 0.05). CONCLUSIONS: Cataract surgery induced ocular surface system failure with a clinically significant persistent inflammatory status (InflammAging) in patients older than 75 years. Prophylactic cyclosporine A 0.1% CE eye drops were associated with improved ocular surface homeostasis and reductions in inflammatory markers.

Tissue Remodeling in Ocular Mucous Membrane Pemphigoid.

Purpose: Ocular mucous membrane pemphigoid (OcMMP) is a rare eye disease characterized by relapsing-remitting or persisting long-lasting inflammatory events associated with progressive scarring. Despite long-term immunomodulating therapy, abnormal fibrosis keeps worsening in patients with OcMMP. This study investigates the fibrotic process in patients with OcMMP, as well as the critical role of the epithelium in modulating the local fibrosis. Methods: In this prospective, observational pilot study, patients affected by long-lasting OcMMP were compared with age- and gender-matched healthy controls. Clinical grading was assessed, and conjunctival biopsy and impression cytology were performed. Conjunctival samples were used for quantifying the expression of transcripts regulating the inflammatory and fibrogenic processes. Results: Ocular surface clinical and functional markers worsened in patients with OcMMP with fibrotic disease progression. In more advanced disease stages, both impression cytologies and conjunctival biopsies revealed increased tissue remodeling and profibrotic markers (α-SMA and TGF-ß), and decreased levels of inflammatory markers (I-CAM1, IL-10, and IL-17). Increased epithelial expression of profibrotic markers and histological changes were detected. Conclusions: Chronic OcMMP is characterized by a progressive, aberrant self-sustaining fibrotic process that worsens clinical signs and symptoms. Conjunctival epithelial cells may transdifferentiate into myofibroblast-like phenotypes when chronically exposed to high levels of inflammation, as in the case of OcMMP. Tissue remodeling markers in OcMMP could be used as early diagnostic, prognostic, and therapeutic biomarkers, harvested in a non-invasive and painless procedure such as impression cytologies.

Ocular surface in posterior segment surgery.

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye.In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients.In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients' symptoms that could manifest in the postoperative time.

Effect of minimonovision in bilateral implantation of a novel non-diffractive extended depth-of-focus intraocular lens: Defocus curves, visual outcomes, and quality of life.

PURPOSE: To evaluate overall patient satisfaction, spectacle independence, visual acuity, and prevalence of optical phenomena following bilateral implantation of a new non-diffractive extended depth-of-focus intraocular lens targeted for minimonovision. METHODS: Multicenter prospective case series. Postoperative far and near visual acuity at 3 months and patient quality of life by NEI-VFQ-25 questionnaire were assessed. Postoperative evaluation included defocus curves analysis, spectacle independence assessment, and recording of photic phenomena. RESULTS: The study enrolled 97 eyes of 59 patients that underwent femtosecond-assisted cataract surgery with AcrySof IQ Vivity intraocular lens implantation. Thirty subjects (60 eyes) were eligible for analysis. After 3 months, postoperative achieved binocular uncorrected visual acuity was -0.03 ± 0.06 logarithm of the minimum angle of resolution for distance, 0.06 ± 0.06 logarithm of the minimum angle of resolution for intermediate, and 0.19 ± 0.03 logarithm of the minimum angle of resolution for near. Defocus curve showed a smooth profile with no abrupt decrease of visual acuity. Minimonovision significantly improved visual acuity compared to when minimonovision was neutralized, for values of defocus curves from -1 to -3 D (p < 0.05). Twenty-six (87%) patients reported complete spectacle independence. High levels of satisfaction for distance and near vision resulted at VFQ-25 questionnaire. Only two patients complained of halos (6.7%) and one of them also of glare (3.3%). CONCLUSIONS: Implantation of this new non-diffractive extended depth-of-focus intraocular lens with minimonovision resulted in satisfying far, intermediate, and near visual acuity with a consistent reduction of spectacle dependence and improvement in patient's quality of life.

Corneal angiogenic privilege and its failure.

The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.

Acanthamoeba Keratitis: Perspectives for Patients.

Purpose: To unveil the long-term prognosis of Acanthamoeba keratitis based on clinical presentation and timing of diagnosis to better inform patients since the first visit regarding their length of treatment, quality of life, and visual function.Methods: Retrospective observational study enrolling patients with Acanthamoeba keratitis from 1994 to 2019. Patients with a complete eye examination and medical records were analyzed. The severity of the disease, the time from onset of symptoms to the appropriate therapeutic regimen, the time until clinical resolution, visual function, and long term follow-up was evaluated. Quality of life was assessed at the last follow-up visit by means of the VFQ-25 questionnaire.Results: Thirty-five patients (40 eyes) were assessed. The overall healing time of patients with Acanthamoeba keratitis was 12.5 ± 3.5 months, while patients with a severe corneal ulcer (stage III) had a significant longer healing time (16.2 ± 3.7 months) compared to patients with stage II (7.04 ± 0.7 months) or I (7.7 ± 1.5 months; p < .05). Patients who received a prompt therapy (<30 days form symptoms onset) had a reduced healing time compared to patients with a delayed diagnosis (p < .01). Quality of life was assessed after a mean of 11.7 ± 4.7 years and it was mildly reduced (86.6 ± 17). Patients that were diagnosed early (<30 days from onset) showed a lower reduction in quality of life than in patients that were diagnosed >30 days from onset. After resolution, 59% of the patients considered unnecessary any further proposed surgical intervention.Conclusions: Delayed diagnosis of Acanthamoeba keratitis and disease severity significantly increases healing time and duration of treatment. The time to diagnosis and disease stage at diagnosis predicts the duration of treatment, the final outcome, quality of life, and the requirement of surgery. These data would allow us to promptly inform patients about long-term disease timeline, future outcomes, improving disease acceptance, and quality of life.

Endoplasmic reticulum stress promotes inflammation-mediated proteolytic activity at the ocular surface.

A growing body of evidence implicates endoplasmic reticulum (ER) stress in the pathogenesis of chronic inflammatory and autoimmune disorders. Here, we demonstrate that the proinflammatory cytokine TNFα stimulates matrix metalloproteinase 9 (MMP9) at the ocular surface through a c-Fos-dependent mechanism of ER stress. We found positive reactivity of the molecular chaperone BiP/GRP78 in conjunctival epithelium of patients with ocular cicatricial pemphigoid and increased levels of BiP/GRP78, sXBP1 and GRP94 in human corneal epithelial cells treated with TNFα. Pharmacological blockade of ER stress in vitro using dexamethasone or the chemical chaperones TUDCA and 4PBA attenuated MMP9 expression and secretion in the presence of TNFα. Moreover, expression analysis of genes associated with inflammation and autoimmunity identified the c-Fos proto-oncogene as a mediator of ER stress responses in epithelial cells. Substantially less TNFα-induced MMP9 expression occurred when c-Fos signaling was suppressed with a function-blocking antibody. Taken together, these results indicate that activation of ER stress contributes to promote inflammation-mediated proteolytic activity and uncovers a target for restoring tissue homeostasis in ocular autoimmune disease.

Biomarkers of Neurodegeneration and Precision Therapy in Retinal Disease.

Vision-threatening retinal diseases affect millions of people worldwide, representing an important public health issue (high social cost) for both technologically advanced and new-industrialized countries. Overall RD group comprises the retinitis pigmentosa, the age-related macular degeneration (AMD), the diabetic retinopathy (DR), and idiopathic epiretinal membrane formation. Endocrine, metabolic, and even lifestyles risk factors have been reported for these age-linked conditions that represent a "public priority" also in this COVID-19 emergency. Chronic inflammation and neurodegeneration characterize the disease evolution, with a consistent vitreoretinal interface impairment. As the vitreous chamber is significantly involved, the latest diagnostic technologies of imaging (retina) and biomarker detection (vitreous) have provided a huge input at both medical and surgical levels. Complement activation and immune cell recruitment/infiltration as well as detrimental intra/extracellular deposits occur in association with a reactive gliosis. The cell/tissue aging route shows a specific signal path and biomolecular profile characterized by the increased expression of several glial-derived mediators, including angiogenic/angiostatic, neurogenic, and stress-related factors (oxidative stress metabolites, inflammation, and even amyloid formation). The possibility to access vitreous chamber by collecting vitreous reflux during intravitreal injection or obtaining vitreous biopsy during a vitrectomy represents a step forward for an individualized therapy. As drug response and protein signature appear unique in each single patient, therapies should be individualized. This review addresses the current knowledge about biomarkers and pharmacological targets in these vitreoretinal diseases. As vitreous fluids might reflect the early stages of retinal sufferance and/or late stages of neurodegeneration, the possibility to modulate intravitreal levels of growth factors, in combination to anti-VEGF therapy, would open to a personalized therapy of retinal diseases.

Lamellar macular holes: monitoring and management strategies.

Lamellar macular holes are a vitreoretinal condition characterized by abnormalities in foveal contour with splitting of the neuroepithelium and often an intact photoreceptor layer. Recent developments in high-resolution imaging have increased our ability to study the details of the vitreoretinal interface and to distinguish between different forms of lamellar holes. A new classification is needed to help clinicians in the management of lamellar macular holes. Some clinicians prefer to observe these clinical entities, especially when visual acuity is maintained or alterations of the photoreceptor layer are present. Nevertheless, lamellar holes may sometimes progress, and visual acuity can deteriorate. On the other hand, surgical treatment may lead to positive anatomical and functional outcomes, but not without risks. This review provides a critical overview of the available data on lamellar macular holes, focusing on diagnosis and managing options.

Inflammatory Stress Causes N-Glycan Processing Deficiency in Ocular Autoimmune Disease.

High levels of proinflammatory cytokines have been associated with a loss of tissue function in ocular autoimmune diseases, but the basis for this relationship remains poorly understood. Here we investigate a new role for tumor necrosis factor α in promoting N-glycan-processing deficiency at the surface of the eye through inhibition of N-acetylglucosaminyltransferase expression in the Golgi. Using mass spectrometry, complex-type biantennary oligosaccharides were identified as major N-glycan structures in differentiated human corneal epithelial cells. Remarkably, significant differences were detected between the efficacies of cytokines in regulating the expression of glycogenes involved in the biosynthesis of N-glycans. Tumor necrosis factor α but not IL-1ß had a profound effect in suppressing the expression of enzymes involved in the Golgi branching pathway, including N-acetylglucosaminyltransferases 1 and 2, which are required for the formation of biantennary structures. This decrease in gene expression was correlated with a reduction in enzymatic activity and impaired N-glycan branching. Moreover, patients with ocular mucous membrane pemphigoid were characterized by marginal N-acetylglucosaminyltransferase expression and decreased N-glycan branching in the conjunctiva. Together, these data indicate that proinflammatory cytokines differentially influence the expression of N-glycan-processing enzymes in the Golgi and set the stage for future studies to explore the pathophysiology of ocular autoimmune diseases.

Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting.

Dry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED-related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase-9, human leucocyte antigen-DR or intercellular adhesion molecule-1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti-inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti-inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.

The challenging management of pediatric corneal transplantation: an overview of surgical and clinical experiences.

PURPOSE: Pediatric keratoplasty is an immense challenge because of the technical complexity of the procedure and the high risk of rejection in young graft recipients. Our aim is to describe the major indications and appropriate timing of corneal transplantation intervention, including a report of our experience and surgical tips, in conjunction with the current literature. METHODS: Review of the literature on indications for keratoplasty in pediatric patients classified as: congenital, traumatic and acquired non-traumatic opacities. We additionally explored the challenges corneal surgeons face in performing this type of surgery and review the most pressing transplant-related problems and their management. RESULTS: Outcomes after pediatric keratoplasty, in terms of visual development, restoration and clarity of the graft, are influenced by peri-operative local and systemic conditions and factors, and by intraoperative management of the transplantation procedure itself. CONCLUSION: Pediatric corneal transplantation is a critical tool for visual restoration and development in young patients with corneal opacities, particularly during the critical period of visual development. Successful management of the significant challenges associated with pediatric keratoplasty requires customized clinical and surgical management of each patient with particular attention paid to proper post-operative rehabilitation.

Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment.

Over the last decades, we have witnessed an increase in the incidence of primary ocular adnexa lymphomas (POALs) probably because advances in imaging techniques have enabled precise biopsies of the tumors. The ocular tissue biopsy, before the initiation of the appropriate treatment, is mandatory and necessary for a correct diagnosis of POALs by the use of immunophenotyping and a correct molecular classification. Only in a minority of cases the ocular adnexa are secondarily affected by a systemic disease. Among the POALs, the most common is the primary extra nodal lymphoma of MALT-type (POAML). POAML is rarely symptomatic in the early phase of the disease. As a consequence, often we see a delay in ophthalmic consultations and diagnosis. The clinical manifestations are heterogeneous and its management requires a multidisciplinary approach involving ophthalmologists, hematologists and radiotherapists.

Toll-Like Receptors and Tissue Remodeling: The Pro/Cons Recent Findings.

The Toll-like Receptor (TLR) family ensures prompt response towards pathogens, protecting the host against infections, and guarantees a realistic balance between protective and detrimental activities. Multiple regulating mechanisms characterize TLR activity that is not limited to innate and adaptive antimicrobial immune responses, as observed in the inflammatory (either infective, allergic, or autoimmune) responses associated with tissue remodeling. Following the insult and the arise of inflammatory response, tissue remodeling takes place and might develop in fibrosis, depending on microenvironment as a result of imbalanced fibroblasts (FBs) and myofibroblasts (myoFBs) activation/survival. The process is driven by an epithelial-fibroblast-immune cell cross-talk. While the main FB function is the matrix metabolism for tissue homeostasis or repair, the myoFB differentiation represents a crucial step in attempting repair of injury. FBs/myoFBs provide more than structural support at site of injury, synthesizing and/or reacting to different cytokines, growth factors, neuromediators and soluble/lipid mediators. TLR-bearing FBs/myoFBs might contribute at the innate immune level, providing a second line of protection/defense as well as being a target/effector cell of tissue remodeling. TLRs might also interfere with acute inflammation as well as with established fibrosis, triggering structural/functional changes in agreement with the genetic background, the site of lesion, the entity of associated infection, the poor blood circulation or the pharmacological treatments, all together strictly influencing tissue repair/remodeling process. This review will focus on the recent findings on TLRs at launch and long-lasting tissue remodeling process, that strongly suggest TLRs as optional targets for future therapies.

Effects of Sex Hormones on Ocular Surface Epithelia: Lessons Learned From Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in women of reproductive age. Although its clinical consequences have been known for a long time to extend beyond the reproductive system, with type-2 diabetes and obesity being the most common, the involvement of the ocular surface in PCOS has been described only more recently. The ocular surface is a morphofunctional unit comprising eyelid margin, tear film, cornea, and conjunctiva. Increasing evidence indicates that these structures are under a sex hormone control and relevant diseases such as ocular allergy and dry eye are often caused by alterations in circulating or local steroid hormones levels. Novel treatments targeting sex hormone receptors on ocular surface epithelial cells are also being developed. In this review we aim to describe the current knowledge on the effects of sex hormones at the ocular surface, with a special focus on the effects of androgen imbalance in PCOS.

NGF Modulates trkANGFR/p75NTR in αSMA-Expressing Conjunctival Fibroblasts from Human Ocular Cicatricial Pemphigoid (OCP).

OBJECTIVE: In a previous study, we reported the upregulation of Nerve Growth Factor (NGF) and trkANGFR expression in Ocular Cicatricial Pemphigoid (OCP), an inflammatory and remodeling eye disease. Herein, we hypothesize a potential NGF-driven mechanism on fibroblasts (FBs) during OCP remodeling events. To verify, human derived OCP-FBs were isolated and characterized either at baseline or after NGF exposure. MATERIALS AND METHODS: Conjunctival biopsies were obtained from 7 patients having OCP and 6 control subjects (cataract surgery). Both conjunctivas and primary FB cultures were characterised for αSMA, NGF and trkANGFR/p75NTR expression. Subcultures were exposed to NGF and evaluated for αSMA, NGF, trkANGFR/p75NTR expression as well as TGFß1/IL4 release. For analysis, early and advanced subgroups were defined according to clinical parameters. RESULTS: OCP-conjunctivas showed αSMA-expressing FBs and high NGF levels. Advanced OCP-FBs showed higher αSMA expression associated with higher p75NTR and lower trkANGFR expression, as compared to early counterparts. αSMA expression was in keeping with disease severity and correlated to p75NTR. NGF exposure did not affect trkANGFR levels in early OCP-FBs while decreased both αSMA/p75NTR expression and TGFß1/IL4 release. These effects were not observed in advanced OCP-FBs. CONCLUSIONS: Taken together, these data are suggestive for a NGF/p75NTR task in the potential modulation of OCP fibrosis and encourages further studies to fully understand the underlying mechanism occurring in fibrosis. NGF/p75NTR might be viewed as a potential therapeutic target.

Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa.

Ocular Adnexal Lymphomas are the first cause of primary ocular malignancies, and among them the most common are MALT Ocular Adnexal Lymphomas. Recently systemic immunotherapy with anti-CD20 monoclonal antibody has been investigated as first-line treatment; however, the optimal management for MALT Ocular Adnexal Lymphomas is still unknown. The present study evaluated retrospectively the outcome of seven consecutive patients with primary MALT Ocular Adnexal Lymphomas, of whom six were treated with single agent Rituximab. All patients received 6 cycles of Rituximab 375 mg/mq every 3 weeks intravenously. The overall response rate was 100%; four patients (67%) achieved a Complete Remission, and two (33%) achieved a partial response. In four patients an additional Rituximab maintenance every 2-3 months was given for two years. After a median follow-up of 29 months (range 8-34), no recurrences were observed, without of therapy- or disease-related severe adverse events. None of the patients needed additional radiotherapy or other treatments. Rituximab as a single agent is highly effective and tolerable in first-line treatment of primary MALT Ocular adnexal Lymphomas. Furthermore, durable responses are achievable with the same-agent maintenance. Rituximab can be considered the agent of choice in the management of an indolent disease in whom the "quality of life" matter is of primary importance.

Sex hormones in allergic conjunctivitis: altered levels of circulating androgens and estrogens in children and adolescents with vernal keratoconjunctivitis.

PURPOSE: Vernal keratoconjunctivitis (VKC) is a chronic allergic disease mainly affecting boys in prepubertal age and usually recovering after puberty. To evaluate a possible role of sex hormones in VKC, serum levels of sex hormones in children and adolescents with VKC were assessed. METHODS: 12 prepubertal and 7 early pubertal boys with active VKC and 6 male patients with VKC in remission phase at late pubertal age and 48 healthy age and sex-matched subjects were included. Serum concentration of estrone, 17 beta-estradiol, dehydroepiandrosterone-sulfate, total testosterone and free testosterone, dihydrotestosterone (DHT), cortisol, delta-4-androstenedione, follicle-stimulating hormone, luteinizing hormone, and sex-hormones binding globuline (SHBG) were evaluated. RESULTS: Serum levels of Estrone were significantly increased in all groups of patients with VKC when compared to healthy controls (P < 0.001). Prepubertal and early pubertal VKC showed a significant decrease in DHT (P = 0.007 and P = 0.028, resp.) and SHBG (P = 0.01 and P = 0.002, resp.) when compared to controls and serum levels of SHBG were increased in late pubertal VKC in remission phase (P = 0.007). CONCLUSIONS AND RELEVANCE: VKC patients have different circulating sex hormone levels in different phases of the disease and when compared to nonallergic subjects. These findings suggest a role played by sex hormones in the pathogenesis and/or activity of VKC.

Cocaine snorting may induce ocular surface damage through corneal sensitivity impairment.

PURPOSE: Cocaine abuse may cause severe ischemic and necrotic tissue damage in several organs, including the eye. However, the cornea is an avascular tissue relying on sensitive nerves for its trophic support, and the pathogenesis of cocaine-induced corneal lesions is unclear. In this study, we aimed to investigate if corneal sensitivity, ocular surface, and tear function are damaged by habitual cocaine snorting. METHODS: Ocular examination, corneal sensitivity, and tear function testing were carried out in 48 cocaine addicts, and in 22 heroin addicts and 30 drug-free age/sex-matched individuals who served as controls. We also performed corneal confocal microscopy, conjunctival impression cytology, and tear sample collection to evaluate corneal and conjunctival morphology, and the presence of cocaine in tears. Statistical analysis was performed to compare groups and to correlate clinical findings with anamnestic data on cocaine use. RESULTS: We observed decreased corneal sensitivity in 26 cocaine addicts, and neurotrophic keratitis in six of them, with corneal damage, absence of symptoms, reduced tear production, and prolonged interblink-time. No significant changes in ocular surface parameters including corneal sensitivity were observed in heroin addicts. The major risk factors for developing cocaine-induced neurotrophic keratitis appeared to be duration and frequency of drug abuse. CONCLUSIONS: A complete ophthalmic evaluation including corneal sensitivity testing should be planned for an optimal management of cocaine addicts, even in the absence of ocular symptoms, to reduce the risk of corneal lesions and consequent vision impairment. Sensory nerve damage should also be evaluated in cocaine-induced lesions of other organs.