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.

HYPERACUTE PSEUDOPHAKIC MACULAR EDEMA VANISHING WITHIN 72 HOURS: A CASE SERIES.

PURPOSE: To report three cases of massive pseudophakic macular edema occurring the day after uneventful cataract surgery and resolving in 24 to 72 hours. METHODS: Observational case series. RESULTS: A 68-year-old woman affected by systemic lupus erythematosus and antiphospholipid syndrome displayed massive macular edema on optical coherence tomography scan one day after uneventful cataract surgery. Routine postoperative topical eye drops (chloramphenicol/betamethasone 4 times a day and bromfenac 2 times a day) were continued without additional medications. Three days later, optical coherence tomography showed a completely recovered, normal fovea. Two similar cases were documented. A 73-year-old man and a 53-year-old man underwent cataract surgery and started the mentioned topical postoperative therapy. Severe macular edema was diagnosed the day after surgery and resolved in 24 and 48 hours, respectively. CONCLUSION: Massive macular edema may occur immediately after uncomplicated cataract and then disappear within 1 to 3 days, without invasive therapies. This is a very significant event that may follow cataract surgery, and that was previously unreported.

Promising High-Tech Devices in Dry Eye Disease Diagnosis.

BACKGROUND: Dry eye disease (DED) is a common and debilitating condition that affects millions of people worldwide. Despite its prevalence, the diagnosis and management of DED can be challenging, as the condition is multifactorial and symptoms can be nonspecific. In recent years, there have been significant advancements in diagnostic technology for DED, including the development of several new devices. METHODS: A literature review of articles on the dry eye syndrome and innovative diagnostic devices was carried out to provide an overview of some of the current high-tech diagnostic tools for DED, specifically focusing on the TearLab Osmolarity System, DEvice Hygrometer, IDRA, Tearcheck, Keratograph 5M, Cornea Dome Lens Imaging System, I-PEN Osmolarity System, LipiView II interferometer, LacryDiag Ocular Surface Analyzer, Tearscope-Plus, and Cobra HD Camera. CONCLUSIONS: Despite the fact that consistent use of these tools in clinical settings could facilitate diagnosis, no diagnostic device can replace the TFOS algorithm.

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.

Ocular Surface Failure in Urban Syndrome.

BACKGROUND: Nowadays, the continuous increase in air pollution has significantly changed air quality, leading to the onset of the so-called urban syndrome (US), an allergic-like conjunctivitis triggered by pollutants. These patients are characterized by persistent dysregulation of ocular surface para-inflammation, causing chronic low-grade inflammation and ocular discomfort, with significant consequences for occupational health and job productivity prospects. This study aims to investigate the effects of topical glycerophosphoinositol (GPI) eye drops on the signs and symptoms of US. METHODS: A multicenter prospective open interventional study was performed. Patients affected by US, enrolled from occupational medicine clinics, were treated with eye drops containing 0.001% GPI in 0.2% HA vehicle three times a day. Ocular surface disease index (OSDI), tear break-up time (T-BUT), Schirmer test, Oxford score, hyperemia and ocular surface symptoms were recorded at patient enrolment (T0), after 1 week (T1) and after 1 month (T2) of treatment. RESULTS: A total of 113 consecutive patients (226 eyes) were included. OSDI score displayed a significant improvement after one week (T0: 39.9 ± 19, T1: 20.8 ± 17.9, T2: 18.4 ± 15.6, p < 0.0001); T-BUT (T0: 5.2 ± 2, T1: 7.7 ± 2.2, T2: 9.7 ± 1.8, p < 0.0001) and Schirmer Test (T0: 6.6 ± 2.4, T1: 9.7 ± 2.7, T2: 12.6 ± 2.6, p < 0.0001) progressively improved from T0 to T2. CONCLUSIONS: trice-daily topic instillation of 0.001% GPI in 0.02% HA vehicle resulted an effective and well tolerated treatment in US patients.

Ocular surface diabetic disease: A neurogenic condition?

PURPOSE: To investigate clinical and inflammatory changes in the ocular surface of insulin-dependent type I diabetic patients. METHODS: Two hundred and nine eyes of 106 patients with diagnosis of type I diabetes were recruited in a prospective observational study. Ocular surface clinical assessment, corneal sensitivity and tear film stability tests were performed to evaluate ocular surface system function. Ocular Surface Disease Index (OSDI) questionnaire was administered to all enrolled subjects. Conjunctival impression cytology specimens were also collected to detect neuromediators and inflammatory molecules. Duration of disease, HbA1c levels and diabetic retinopathy stage were recorded. RESULTS: Corneal sensitivity assessed by Cochet-Bonnet esthesiometer was reduced in patients with more chronic disease, higher HbA1c levels and proliferative diabetic retinopathy. Tear break-up time (TBUT) was reduced in subjects with long-standing diabetes or with more severe retinopathy. OSDI questionnaire scores showed direct correlation with increased HbA1c values. Significant increase of NPY, STAT-5 and ICAM-1 was found in diabetic patients compared to healthy controls. A direct correlation between NPY concentration and ICAM-1 values in patients with type I diabetes was demonstrated. CONCLUSIONS: Patients with long-standing type I diabetes showed chronic inflammation of the ocular surface, due to neurogenic dysregulation of para-inflammatory homeostatic mechanisms. These patients with ocular surface system failure complained of ocular discomfort but had modest reduction of corneal sensitivity and no signs of neurotrophic keratopathy. Disease duration, increased HbA1c levels and severe diabetic retinopathy appear the most critical factors.

A global perspective of pediatric non-viral keratitis: literature review.

PURPOSE: This focused review aims to explore pediatric non-viral keratitis and to compare associated risk factors, etiologies, antibiotic susceptibilities, empiric treatments and outcomes. METHODS: The authors performed a literature research for articles, published on PubMed, Google Scholar, Scopus and Embase online library, relevant to pediatric keratitis etiology, risk factors, antibiotic susceptibilities, treatment and outcomes. From the bibliography of selected articles, additional relevant articles were also considered. Of 34 articles identified, 21 were suitable for the purpose of this review. RESULTS: Several risk factors are noted in the field of pediatric keratitis. Trauma is the most common in developing countries, while contact lenses wear is seen in developed economies. Previous ocular conditions and systemic diseases also contribute. Associated malnourishment and vitamin A deficit are fraught with a catastrophic prognosis. Among causative organisms, bacteria are more common than fungi and protozoa. Gram-positive organisms are predominant where contact lenses use is infrequent. Pseudomonas aeruginosa is often the leading pathogen in developed countries and is strongly associated with contact lens wear or malnourishment. Fungi are common in the tropics and associated with trauma. Levofloxacin seems the more effective empirical treatment when bacteria are suspected, but there is no agreement on a standard of care. CONCLUSION: There are differences in etiologic patterns between developing and developed countries and different regions globally. Risk factors follow the same trend; however, there is no standard regimen being followed for empirical treatment of pediatric infectious keratitis. Associated malnourishment and vitamin A deficiency result in poorer outcomes.

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.

Age-Related Changes to Human Tear Composition.

Purpose: We characterize age-associated alterations in the expression of inflammatory mediators and tissue remodeling factors in human tears. Methods: A total of 75 consecutive volunteers (32 male/44 female; 19-93 years) underwent clinical assessment of ocular surface status, ocular surface disease index (OSDI) grading and tear sampling. The volunteers were categorized into three groups: young (18-40 years), middle-aged (41-60 years), and old (>60 years). Total protein profiles and chip-based protein array evaluations were conducted to investigate the expression of 60 potential candidates, including pro-/anti-inflammatory mediators and tissue remodeling factors. Appropriate validations were performed using conventional assays. Multiple comparisons for regression between potential candidates and age were performed, as well as statistical analyses among the three age groups. Nonpooled samples were used for quantifications. Results: Pearson analysis of chip-arrays identified 9 of 60 potential candidates. Specifically, IL-8, IL-6, and regulated on activation, normal T cell expressed and secreted (RANTES; P < 0.0083) protein as well as matrix metalloproteinase (MMP)-1, IL-3, and TNF-α (P < 0.05) correlated positively with aging. MIP-3ß showed an opposite tendency. Western blot and ELISA analysis corroborated the array data. OSDI grading did not correlate with aging. Conclusions: Dynamic changes to tear protein profiles occur with aging. Our study identifies the expression of IL-8, IL-6, RANTES, MMP-1, and MIP-3ß as increasing with age. These select inflammatory and matrix remodeling factors may be relevant to the development of novel diagnostic tools and therapeutics in the context of age-related ocular surface disease.

Quiescent and Active Tear Protein Profiles to Predict Vernal Keratoconjunctivitis Reactivation.

OBJECTIVE: Vernal keratoconjunctivitis (VKC) is a chronic recurrent bilateral inflammation of the conjunctiva associated with atopy. Several inflammatory and tissue remodeling factors contribute to VKC disease. The aim is to provide a chip-based protein analysis in tears from patients suffering from quiescent or active VKC. METHODS: This study cohort included 16 consecutive patients with VKC and 10 controls. Participants were subjected to clinical assessment of ocular surface and tear sampling. Total protein quantification, total protein sketch, and protein array (sixty protein candidates) were evaluated. RESULTS: An overall increased Fluorescent Intensity expression was observed in VKC arrays. Particularly, IL1ß, IL15, IL21, Eotaxin2, TACE, MIP1α, MIP3α, NCAM1, ICAM2, ßNGF, NT4, BDNF, ßFGF, SCF, MMP1, and MMP2 were increased in quiescent VKC. Of those candidates, only IL1ß, IL15, IL21, ßNGF, SCF, MMP2, Eotaxin2, TACE, MIP1α, MIP3α, NCAM1, and ICAM2 were increased in both active and quiescent VKC. Finally, NT4, ßFGF, and MMP1 were highly increased in active VKC. CONCLUSION: A distinct "protein tear-print" characterizes VKC activity, confirming some previously reported factors and highlighting some new candidates common to quiescent and active states. Those candidates expressed in quiescent VKC might be considered as predictive indicators of VKC reactivation and/or exacerbation out-of-season.

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.

In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis.

PURPOSE: Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis. METHODS: Eight patients (6 male, 2 female; mean age 45.7+/-17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0-3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity. RESULTS: An improvement in TSS (4.5+/-1.1 vs 2.7+/-1.5) and TSyS (6.6+/-1.3 vs. 3.1+/-1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed. CONCLUSIONS: This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation.

Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva.

PURPOSE: To evaluate the role of nerve growth factor (NGF) in remodeling processes of vernal keratoconjunctivitis (VKC). VKC is a chronic inflammatory disorder of the conjunctiva and is characterized by marked tissue remodeling. NGF, a pleiotrophic factor with documented profibrogenic activities, is produced by inflammatory and structural cells populating the VKC conjunctiva and is increased in the serum and tears of VKC patients. METHODS: Primary cultures of VKC-derived fibroblasts (VKC-FBs) were exposed to increasing NGF concentrations (1-500 ng/ml) to evaluate and compare the expression of alpha-smooth muscle actin (alphaSMA, a defining myofibroblast marker), collagens (types I and IV), and metalloproteinases and tissue inhibitors (MMP9/TIMP1, MMP2/TIMP2) at the biochemical as well as molecular levels. RESULTS: Endogenous NGF was increased in the VKC-FB supernatant, as compared to healthy-FB supernatant. VKC-FBs expressed alphaSMA and increased types I and IV collagens. VKC-FBs, and in particular all alphaSMA positive cells, expressed both trkA(NGFR) and p75(NTR), while healthy-FBs only expressed trkA(NGFR). Exogenous NGF did not change alphaSMA expression, while alphaSMA expression was enhanced by specific neutralization of p75(NTR). NGF (10 ng/ml) exposure significantly decreased type I collagen expression, without affecting type IV collagen, and increased MMP9mRNA and protein. CONCLUSIONS: The autocrine modulation of differentiation and response of VKC-FBs to NGF exposure with downregulation of type I collagen and upregulation of MMP9 expression supports a relevant role for NGF in tissue remodeling of VKC.

Clinical and cytological findings in limbal stem cell deficiency.

PURPOSE: To evaluate and relate the clinical (including corneal sensitivity and tear function) and cytological (presence of goblet cells and cytokeratin 3- and 19-positive cells) features of limbal stem cell deficiency (LSCD). METHODS: Twenty-nine patients (44 eyes) with a clinical diagnosis of LSCD participated in this study. Corneal signs (epithelial alterations, superficial neovascularisation and stromal scarring) and cytological findings (presence of goblet cells and cytokeratins 3 and 19) were evaluated and scored (from 0 to 3) from each of the five corneal sectors. Corneal sensitivity (Cochet-Bonnet aesthesiometer) and tear function (Schirmer test and BUT) were also assessed. Cytological scores were correlated statistically with both corneal signs and sensitivity values. RESULTS: Cytokeratin 19-positive cells were found in 82% of corneal impression cytology samples, while goblet cells were identified in only 59% of these same samples. Cytokeratin 3-positive cells were present in 61% of LSCD eyes and in all unaffected eyes. Corneal sensitivity was significantly decreased in affected eyes compared with contralateral, healthy eyes (1.6+/-1.7 cm versus 5.7+/-0.3 cm). Tear function tests did not show significant changes. In LSCD eyes, goblet cells and cytokeratin 19-positive cells on the corneal surface were significantly correlated to corneal epithelial alterations and to corneal superficial neovascularisation (p<0.001). Corneal cytokeratin 3-positive cells were inversely related to epithelial alterations (p=0.003). Corneal sensitivity was decreased in corneal sectors with epithelial alterations (p<0.001), neovascularisation (p<0.001) and stromal abnormalities (p=0.049), and was indirectly related to the presence of goblet cells (p=0.005) and cytokeratin 19-positive cells (p<0.001). CONCLUSION: This study confirmed the importance of cytological tests in the diagnosis of LSCD. Furthermore, the absence of goblet cells may not exclude corneal conjunctivalisation as demonstrated by cytokeratin 19 immunostaining. Lastly, corneal conjunctivalisation was associated with zone-specific impairment in corneal sensitivity.

Efficacy of topical nerve growth factor treatment in dogs affected by dry eye.

BACKGROUND: Preliminary data show that nerve growth factor (NGF) may improve tear production in humans. We evaluated the efficacy of topical NGF treatment in dogs who developed dry eye after the excision of the third eyelid lacrimal gland. METHODS: English Bulldogs (2- to 6-year-old males and females) that had undergone the surgical removal of the prolapsed lacrimal gland of the third eyelid in both eyes at the age of 3-6 months developed chronic keratoconjunctivitis sicca associated with a decrease of Schirmer tear test I values after at least 1 year. One eye, randomly selected, of each dog was treated twice daily with 100 microl of NGF ointment for 1 month, while the fellow eye was used as control and treated with the ointment vehicle only. At baseline and after 1 month of NGF treatment the following examinations were performed: corneal evaluation by slit lamp, fluorescein staining, Schirmer tear test I, tear ferning test, corneal esthesiometry by cotton swab and conjunctival impression cytology. RESULTS: Topical application of NGF caused a significant improvement of all the evaluated parameters compared with baseline values. In contrast, in the control eyes there was no significant difference between the values measured before and after treatment. In particular, after NGF treatment superficial punctate keratopathy was resolved, corneal haze was reduced from stage 4 to stage 2 and Schirmer test values increased (17.2+/-1.7 mm/min vs 4.5+/-1.3 mm/min; p<0.05), as did the tear mucous component (as demonstrated by ferning test: 2.0+/-0.0 vs 4.0+/-0.0; p<0.05); conjunctival impression cytology evaluation demonstrated the presence of numerous mucous filaments and a significant increase in conjunctival goblet cell density (102.7+/-68.3 vs. 18.2+/-14.3 cell x field; p<0.05). Topical NGF treatment improved corneal sensitivity in two of three eyes. CONCLUSIONS: This open study suggests that topical application of NGF may enhance the production and functional characteristics in tear film, with an improvement of ocular surface signs in dogs with surgically induced dry eye. These results suggest the possibility of performing further, larger, controlled studies.

Nerve growth factor and the immune system: old and new concepts in the cross-talk between immune and resident cells during pathophysiological conditions.

PURPOSE OF REVIEW: This review provides an overview of nerve growth factor and its involvement in the immune system. Furthermore, recent data are provided revealing new important insights into the mechanisms of action of nerve growth factor in allergic reaction. RECENT FINDINGS: Recent studies on the effects of nerve growth factor on the immune cells involved allergic reaction, and on the potential role of nerve growth factor in tissue remodelling are presented. SUMMARY: Nerve growth factor has an extended function from the nervous system to a wide range of activities in the immune system. Several papers have highlighted the role of the factor in allergic inflammation. This review describes old and new concepts of nerve growth factor in the immune system: the relation between nerve growth factor and the main cells taking part in allergic inflammatory disorders, structural cells, mediators and cytokines/chemokines, as well as the mechanisms leading to nerve growth factor increase. Understanding these complex mechanisms will introduce new therapeutic approaches for nerve growth factor in the immune system, in addition to those already established in the nervous system.

Allergic chronic inflammation of the ocular surface in vernal keratoconjunctivitis.

PURPOSE OF REVIEW: The purpose of this review is to describe the new immunopathologic features of vernal keratoconjunctivitis: the involvement of cytokines, growth factors, cells, mediators and neurotransmitters, as well as the mechanism leading to tissue remodelling. RECENT FINDINGS: Vernal keratoconjunctivitis is an allergic eye disease affecting young boys living in a warm climate. It is characterized by conjunctival giant papillae, hyperemia and frequent involvement of the cornea. Approximately 50% of the patients with vernal keratoconjunctivitis do not have a family or medical history of atopic diseases, and do not show IgE sensitization, suggesting that this disease is not solely IgE mediated. Vernal keratoconjunctivitis is a Th2 lymphocyte driven disease with a Th2 cytokine derived pattern, increased levels of mRNA for IL-3, IL-4, IL-5 and IL-13. Th2 lymphocytes induce IgE hyperproduction, activation of mast cells, eosinophils, neutrophils and their toxic products. An overexpression of adhesion molecules, RANTES, eotaxin and metalloproteinases contribute to chronic inflammation. A role for substance P and nerve growth factor has been postulated, as well as for other growth factors (epidermal growth factor, fibroblast growth factor and transforming growth factor beta 1) that induce fibroblast growth and new collagen production. Recent studies have also pointed out the role of resident conjunctival cells, such as epithelial cells and fibroblasts, in the inflammatory and remodelling process of vernal keratoconjunctivitis. The pathogenesis of the condition is probably multifactorial, with the interaction of the immune, nervous and endocrine systems. SUMMARY: Vernal keratoconjunctivitis is a chronic inflammatory and potentially blinding disease. Understanding of the complex interactions and cross talk between cells, cytokines and other mediators is relevant for new therapeutic approaches.

Preservative-free diclofenac sodium 0.1% for vernal keratoconjunctivitis.

PURPOSE: The aim of this study is to evaluate the efficacy of prolonged treatment with preservative-free diclofenac sodium 0.1% eye drops in patients with vernal keratoconjunctivitis (VKC). METHODS: A prospective open study was performed in 22 patients with VKC treated with preservative-free diclofenac sodium 0.1% eye drops. Patients used the eye drops four times daily in both eyes for 120 days. Signs (papillae, hyperaemia and corneal lesions) and symptoms (itching, redness and photophobia) of the ocular surface were graded and statistically evaluated before and after treatment by a non-parametric test (Mann-Whitney U-test). RESULTS: Forty per cent of the patients showed an improvement in their symptoms at the end of the treatment. Total signs and symptoms scores were significantly decreased at the end of treatment compared with the baseline values (from 6.13+/-1.45 to 0.81+/-0.90 and from 5.40+/-1.18 to 2.63+/-0.95, respectively; P<0.001). Significant decreases in conjunctival redness (P<0.001), itching (P<0.001) and photophobia (P<0.001 ) were observed at the end of treatment. Conjunctival hyperaemia was significantly reduced (P<0.001) at the end of treatment, while no significant differences were observed for corneal lesions and for papillary size. No patient showed exacerbation of the disease during the treatment. CONCLUSION: VKC is a chronic disease that requires prolonged treatment to control the inflammatory process. Our preliminary study demonstrates the efficacy and safety of preservative-free diclofenac sodium 0.1% eye drops in controlling the signs and symptoms of VKC in prolonged treatment.