Adalimumab in Patients with Active Noninfectious Uveitis.

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).

Assessment of Confocal Microscopy for the Diagnosis of Polymerase Chain Reaction-Positive Acanthamoeba Keratitis: A Case-Control Study.

PURPOSE: To determine in vivo confocal microscopy diagnostic criteria to diagnose Acanthamoeba keratitis (AK) using polymerase chain reaction (PCR) as the reference diagnostic technique. DESIGN: Retrospective case-control study. Data were recorded prospectively and analyzed retrospectively. PARTICIPANTS: Fifty patients with PCR-positive AK (study group) and 50 patients with bacterial, fungal, viral, or immune keratitis featuring negative Acanthamoeba PCR results (control group). METHODS: In vivo confocal microscopy performed at the acute stage of keratitis. MAIN OUTCOME MEASURES: Presence of in vivo confocal microscopy images suggestive of AK. Multivariate logistic regression was used to determine the relationship between types of images and presence of PCR-positive AK. RESULTS: The following 4 types of images were associated significantly with PCR-positive AK (P < 0.05): bright spots (round or ovoid hyperreflective objects with no double wall; diameter, <30 µm); target images (hyperreflective objects with hyporeflective halo; diameter, <30 µm); clusters of hyperreflective objects (diameter, <30 µm); and trophozoite-like objects (diameter, >30 µm). Specificity of both target and trophozoite images was 100%. This figure was 98.2% for clusters and 48.2% for bright spots. If the diagnosis of AK was made on presence of target images, clusters or trophozoite images (at least 1 of the 3 features), the positive predictive value of confocal microscopy was 87.5% and the negative predictive value was 58.5%. CONCLUSIONS: Acanthamoeba keratitis is a serious vision-threatening disease. In vivo confocal microscopy can help in this challenging diagnosis, especially when PCR is delayed, shows negative results, or is not available. Target images and trophozoite-like images are pathognomonic of AK. Clusters of hyperreflective objects are highly specific of AK. However, the overall sensitivity of in vivo confocal microscopy features of AK is low. In addition to the clinical features, microbiological tests (direct examination and cultures of corneal scrapings), and PCR, in vivo confocal microscopy allows for more rapid diagnosis and treatment initiation, potentially leading to an improved outcome.

Keratoneuritis is not pathognomonic of Acanthamoeba keratitis: a case report of Pseudomonas keratitis.

The presence of keratoneuritis in a radial pattern is considered to be a virtually pathognomonic sign of Acanthamoeba keratitis. We report a case of a massive keratoneuritis as a presenting sign in Pseudomonas keratitis in a contact lens wearer, thereby further challenging this concept.

Myopia management algorithm. Annexe to the article titled Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

Myopia is becoming increasingly common in young generations all over the world, and it is predicted to become the most common cause of blindness and visual impairment in later life in the near future. Because myopia can cause serious complications and vision loss, it is critical to create and prescribe effective myopia treatment solutions that can help prevent or delay the onset and progression of myopia. The scientific understanding of myopia's causes, genetic background, environmental conditions, and various management techniques, including therapies to prevent or postpone its development and slow its progression, is rapidly expanding. However, some significant information gaps exist on this subject, making it difficult to develop an effective intervention plan. As with the creation of this present algorithm, a compromise is to work on best practices and reach consensus among a wide number of specialists. The quick rise in information regarding myopia management may be difficult for the busy eye care provider, but it necessitates a continuing need to evaluate new research and implement it into daily practice. To assist eye care providers in developing these strategies, an algorithm has been proposed that covers all aspects of myopia mitigation and management. The algorithm aims to provide practical assistance in choosing and developing an effective myopia management strategy tailored to the individual child. It incorporates the latest research findings and covers a wide range of modalities, from primary, secondary, and tertiary myopia prevention to interventions that reduce the progression of myopia.

Vernal keratoconjunctivitis in school children in Rwanda: clinical presentation, impact on school attendance, and access to medical care.

OBJECTIVE: We sought to describe the clinical presentation, effect on visual acuity, impact on school attendance, and access to appropriate eye care in children with vernal keratoconjunctivitis (VKC) in Rwanda (Central Africa). DESIGN: Case-control study nested within a cross-sectional survey. PARTICIPANTS: We examined 3041 children; 121 had VKC. METHODS: Primary schools were randomly selected and children were interviewed using a questionnaire on VKC-related symptoms. Data on health-seeking behavior and school attendance were recorded. Children received a full eye examination, including visual acuity using a LogMar E Chart. MAIN OUTCOME MEASURES: Description of the clinical findings, unaided visual acuity, prior attendance for medical eye care, and the impact of VKC on school attendance. RESULTS: Of the 121 children with VKC, 119 (98.4%) had only limbal disease. Ocular itching (n = 101; 83.5%) was the predominant symptom and this was seasonal in 66 children (65.4%), constant but with variable intensity in 18 (17.8%), and constant with constant intensity in 17 children (16.8%). Children with VKC were >6 times more likely to have corneal astigmatism >2 diopters in their worse eye (odds ratio [OR], 6.31; 95% confidence interval [CI], 3.26-12.26; P<0.001) than controls. Eight affected eyes had astigmatism >4 diopters or irregular astigmatism incompatible with autokeratometry. Although 4 eyes (1.7%) had uncorrected low vision from VKC-induced corneal astigmatism or keratoconus, only 1 child was visually impaired in both eyes. School nonattendance for an ocular reason during the last 3 months was 5 times more likely in children with VKC (n = 44; 36.4%) than among those without (n = 297; 10.2%; OR, 5.04; 95% CI, 3.40-7.47; P < 0.001). Repeating a school year or having ever dropped out of school was not more common among children with VKC than those without. Medical eye care had been sought by 54 (44.6%) children with VKC. CONCLUSIONS: This survey of prevalence and treatment of VKC in an African community adds to the argument for better primary eye care, including a safe topical medication. Long-term follow-up of this cohort is required to ascertain the overall risk of sight-threatening complications.

Efficacy and safety of abatacept to treat active birdshot uveitis: a prospective open label interventional proof-of-concept trial.

BACKGROUND/AIMS: Birdshot uveitis (BU) is a chronic autoimmune posterior uveitis, mostly affecting middle-aged Caucasians. There is a strong association with HLA-A29 and T-cell activation. Safety and efficacy of abatacept, an inhibitor of T-cell costimulation, is tested in active BU. METHODS: Fifteen patients with active BU were treated with monotherapy of weekly subcutaneous injections of abatacept 125 mg/mL. Time-to-treatment failure was evaluated as a primary outcome. The secondary objective was to evaluate the utility of different outcome measures to monitor disease activity. Safety was evaluated by adverse event reporting and serial blood analyses. RESULTS: At the year-1 endpoint, there was significant improvement in vitreous haze grade (p=0.0014), central choroidal thickness (CCT) (p=0.0011), Fluorescein Angiography (FA) Score (p=0.0014), Indocyanine Green Angiography (ICGA) Score (p<0.001) and total dual FA-ICGA Score (p<0.001). Best corrected visual acuity (BCVA) (p=0.8354) and central retinal thickness (CRT) (p=0.3549) did not change significantly. There were no serious adverse events reported. In total, 4 out of 15 patients left the trial during year 1 of whom 2 experienced treatment failure. CONCLUSIONS: Abatacept is very efficacious to treat both retinal vasculitis and choroiditis in patients with BU and is well tolerated. BCVA and CRT are inadequate to monitor disease activity. On the other hand, CCT is a promising non-invasive tool to detect treatment response in early active BU and dual FA-ICGA Score is very helpful to evaluate retinal vasculitis and choroiditis quantitatively. TRIAL REGISTRATION NUMBER: NCT03871361.

Biallelic mutation of BEST1 causes a distinct retinopathy in humans.

We describe a distinct retinal disorder, autosomal-recessive bestrophinopathy (ARB), that is consequent upon biallelic mutation in BEST1 and is associated with central visual loss, a characteristic retinopathy, an absent electro-oculogram light rise, and a reduced electroretinogram. Heterozygous mutations in BEST1 have previously been found to cause the two dominantly inherited disorders, Best macular dystrophy and autosomal-dominant vitreoretinochoroidopathy. The transmembrane protein bestrophin-1, encoded by BEST1, is located at the basolateral membrane of the retinal pigment epithelium in which it probably functions as a Cl(-) channel. We sequenced BEST1 in five families, identifying DNA variants in each of ten alleles. These encoded six different missense variants and one nonsense variant. The alleles segregated appropriately for a recessive disorder in each family. No clinical or electrophysiological abnormalities were identified in any heterozygotes. We conducted whole-cell patch-clamping of HEK293 cells transfected with bestrophin-1 to measure the Cl(-) current. Two ARB missense isoforms severely reduced channel activity. However, unlike two other alleles previously associated with Best disease, cotransfection with wild-type bestrophin-1 did not impair the formation of active wild-type bestrophin-1 channels, consistent with the recessive nature of the condition. We propose that ARB is the null phenotype of bestrophin-1 in humans.

Eyelashes on an extruding porous polyethylene orbital implant.

This photo essay describes a patient with eyelashes perpendicular to the extruding part of a porous polyethylene orbital implant. The upright position of these eyelashes created the impression of growth on the extruding implant, but they are lost eyelashes that became entrapped in the pores of the implant.

HLA-A29 Birdshot Retinochoroiditis in Its 5th Decade: Selected Glimpses into the Intellectual Meanderings and Progresses in the Knowledge of a Long-Time Misunderstood Disease.

The appraisal of HLA-A29 birdshot retinochoroiditis (BRC) was fraught with pitfalls and misunderstandings. Progress in investigational methods has led to better knowledge and management of the disease. Our aim was to assess some of the steps that have led to better characterisation of the clinical entity of BRC. We performed a literature search analysing the relevant progress in disease origin, investigational and imaging methods, clinicopathology and classification, diagnostic criteria and management. Following developments were judged essential in the better appraisal and understanding of the disease: (1) new immunopathological hypotheses regarding the role of endoplasmic reticulum peptidases, (2) the essential importance of HLA testing, (3) relevant imaging modalities among which indocyanine green angiography is crucial, (4) diagnostic criteria that allow early diagnosis and (5) need of an early prolonged, as well as aggressive treatment combining more than one immunosuppressive agent. Based on these findings it is now possible to better define BRC, an indolent however severe disease, unlike thought before, involving the choroidal stroma and the retina independently and concomitantly that can be diagnosed early thanks to indocyanine green angiography and should be treated early and relentlessly.

Update and guidance on management of myopia. European Society of Ophthalmology in cooperation with International Myopia Institute.

The prevalence of myopia is increasing extensively worldwide. The number of people with myopia in 2020 is predicted to be 2.6 billion globally, which is expected to rise up to 4.9 billion by 2050, unless preventive actions and interventions are taken. The number of individuals with high myopia is also increasing substantially and pathological myopia is predicted to become the most common cause of irreversible vision impairment and blindness worldwide and also in Europe. These prevalence estimates indicate the importance of reducing the burden of myopia by means of myopia control interventions to prevent myopia onset and to slow down myopia progression. Due to the urgency of the situation, the European Society of Ophthalmology decided to publish this update of the current information and guidance on management of myopia. The pathogenesis and genetics of myopia are also summarized and epidemiology, risk factors, preventive and treatment options are discussed in details.

The Changing Global Epidemic of HIV and Ocular Disease.

Purpose: Overview of the evolving epidemiology of human immunodeficiency virus (HIV)-related ocular disease over time. Method: Narrative review. Results: HIV enhances susceptibility to opportunistic eye infections, has direct pathogenic effects, and places patients at risk of immune recovery inflammatory syndromes in previously infected eyes after starting highly-active antiretroviral therapy (HAART). Widespread availability of HAART has resulted in a decrease of infectious ocular conditions such as cytomegalovirus retinitis, toxoplasmic retinitis, squamous cell carcinoma of the conjunctiva, and microvascular retinopathy. However, large coexisting burdens of tuberculosis, herpesvirus infection and syphilis (among others) continue to contribute to the burden of ocular disease, especially in low-resource settings. Growing risks of cataract, retinopathy and retinal nerve fiber thinning can affect patients with chronic HIV on HAART; thought due to chronic inflammation and immune activation. Conclusion: The changing epidemic of ocular disease in HIV-infected patients warrants close monitoring and identification of interventions that can help reduce the imminent burden of disease.

Cutting and pasting corneas: combination of a corneal allograft with relocation of a crescent of autologous corneal tissue in therapeutic penetrating keratoplasty.

PURPOSE: A therapeutic penetrating keratoplasty (TPKP) technique that achieves satisfactory visual rehabilitation with a minimal risk of rejection is described. METHODS: A patient presented with a central corneal perforation in the left eye extending to the temporal limbus. We performed a novel surgical procedure, in which a corneal allograft was combined with relocation of a crescent of autologous corneal tissue. RESULTS: The TPKP placed the optical zone of the donor cornea over the center of the entrance pupil. The chances of an immunologic rejection were minimized by intercalating a crescent of autologous tissue between the allograft and the limbal vessels. CONCLUSION: The combination of an allograft with a crescent of autologous corneal tissue minimizes the disadvantages associated with eccentric or oversized trephination.

Fuchs' Uveitis Syndrome: No Longer a Syndrome?

PURPOSE: Rubella virus (RV) has a central role in the etiopathogenesis of Fuchs' uveitis syndrome (FUS). We aim to offer new insights by comprehensive analysis of recent laboratory and epidemiologic data. METHODS: We conducted a literature search for laboratory data and papers on etiopathogenesis. RESULTS: Aqueous humour samples of FUS patients show immunoreactivity to RV, in a specific and sensitive manner. Identification of RV genome confirm intraocular infection in a subset of FUS patients. Epidemiologic findings further support causality. The clinical spectrum of RV-associated uveitis is similar but not identical to FUS. FUS eyes exhibit a predominance of CD8 + T cells, high IFN-? and IL-10 levels. CONCLUSIONS: RV is the leading cause of FUS. Cytokine-based findings mirror a viral etiology and chronic low-grade inflammation. RV-associated FUS represents a common pathway of intraocular RV inoculation after congenital or acquired infection. Other causes, including HSV and CMV, may lead to FUS.

Unilateral proptosis and blindness caused by meningioma in a patient treated with cyproterone acetate.

Cyproterone has antiandrogenic, antigonadotropic, and progestagenic activity. High-dose preparations are used for treatment of prostate cancer and for treatment of hypersexuality. We describe a patient who was referred to our clinic with slowly progressive unilateral proptosis and blindness of the left eye. He had been treated with high-dose cyproterone actate (CPA) for 23 years. An obvious proptosis and exodeviation of his left eye was noted on ophthalmic examination. Fundoscopy showed left optic atrophy. The literature suggests a link between long-term high-dose exogenous progesterone agonist exposure and the progression and/or development of meningioma. MRI of the brain was performed and revealed multiple meningiomas. One large meningioma located in the anterior temporal lobe extended into the left orbit and caused the proptosis and blindness. Treatment with CPA was stopped and follow-up imaging 11 months later showed a significant decrease in size of the largest meningiomas.

Vascular dysregulation in normal-tension glaucoma is not affected by structure and function of the microcirculation or macrocirculation at rest: a case-control study.

In normal-tension glaucoma (NTG), optic nerve damage occurs despite a normal intraocular pressure. Studies implicating systemic blood pressure or, more recently, arterial stiffness in the pathophysiology of NTG have produced conflicting results. Our aim was to investigate whether NTG is associated with alterations in the macrocirculation or microcirculation, cardiac function, and peripheral and central hemodynamics. Thirty patients with NTG (mean age 65 years, range 46-79) and 33 healthy subjects (mean age 67 years, range 42-79) matched for age and sex were included in the study. Exclusion criteria (for both cases and controls) were history of cardiovascular disease, diabetes mellitus, severe hypertension, and hypercholesterolemia. Aortic stiffness was measured using carotid-femoral pulse wave velocity (PWV), central hemodynamics using carotid artery applanation tonometry, and diameter, stiffness, and intima-media thickness (IMT) of the carotid and femoral artery using echo-tracking. Total peripheral resistance index (TPRI) was derived from mean arterial pressure and cardiac index, measured using ultrasound. There were no statistically significant differences in arterial structure nor function between NTG patients and age and sex-matched controls. NTG versus controls, respectively: brachial blood pressure 126 ± 15/77 ± 8 versus 127 ± 16/76 ± 7 mm Hg, P = 0.81; carotid-femoral PWV 9.8 ± 2.1 versus 10.1 ± 1.9 m/s, P = 0.60; TPRI 1833 ± 609 versus 1779 ± 602 dyne.s/cm5/m2, P = 0.79; and carotid IMT 0.65 ± 0.14 versus 0.68 ± 0.13 mm, P = 0.39. This study could not show an association of NTG with altered IMT, arterial stiffness, total peripheral resistance, cardiac output, and peripheral or central hemodynamics at rest. Although the majority of these NTG patients do exhibit symptoms of vascular dysregulation, in the present study this was not translated into alterations in the microcirculation or macrocirculation at rest.

Novel FRMD7 Mutations and Genomic Rearrangement Expand the Molecular Pathogenesis of X-Linked Idiopathic Infantile Nystagmus.

PURPOSE: Idiopathic infantile nystagmus (IIN; OMIM 31700) with X-linked inheritance is one of the most common forms of infantile nystagmus. Up to date, three X-linked loci have been identified, Xp11.4-p11.3 (calcium/calmodulin-dependent serine protein kinase [CASK]), Xp22 (GPR143), and Xq26-q27 (FRMD7), respectively. Here, we investigated the role of mutations and copy number variations (CNV) of FRMD7 and GPR143 in the molecular pathogenesis of IIN in 49 unrelated Belgian probands. METHODS: We set up a comprehensive molecular genetic workflow based on Sanger sequencing, targeted next generation sequencing (NGS) and CNV analysis using multiplex ligation-dependent probe amplification (MLPA) for FRMD7 (NM_194277.2) and GPR143 (NM_000273.2). RESULTS: In 11/49 probands, nine unique FRMD7 changes were found, five of which are novel: frameshift mutation c.2036del, missense mutations c.801C>A and c.875T>C, splice-site mutation c.497+5G>A, and one genomic rearrangement (1.29 Mb deletion) in a syndromic case. Additionally, four known mutations were found: c.70G>A, c.886G>C, c.910C>T, and c.660del. The latter was found in three independent families. In silico predictions and segregation testing of the novel mutations support their pathogenic effect. No GPR143 mutations or CNVs were found in the remainder of the probands (38/49). CONCLUSIONS: Overall, genetic defects of FRMD7 were found in 11/49 (22.4%) probands, including the first reported genomic rearrangement of FRMD7 in IIN, expanding its mutational spectrum. Finally, we generate a discovery cohort of IIN patients potentially harboring either hidden a variation of FRMD7 or mutations in genes at known or novel loci sustaining the genetic heterogeneity of IIN.

Role of natural killer cells in the rejection process of corneal allografts in rats.

BACKGROUND: The exact mechanism of human corneal allograft rejection, which is the major cause of corneal transplant failure, remains unclear. We investigated the role of natural killer (NK) cells in rat corneal allograft rejection by examining the aqueous humor (AH) cell infiltrate on different postoperative days. METHODS: Flow cytometric analysis was performed on the AH and submandibular draining lymph node (DLN) cells before transplantation and at different time points thereafter. In addition, we performed functional cytotoxicity assays with cells present in the AH during corneal rejection. RESULTS: We demonstrated a gradual increase in the absolute cell number of different hematopoietic subpopulations in the AH after allogeneic cornea transplantation. CD3CD4 cells, mainly monocytes and macrophages, were the predominant subpopulation 2 days after transplantation, followed by a successive relative increase of CD4 T cells, CD8 T cells, CD161 T cells, and NK cells. NK and CD161 T cells were present at a 10- to 15-fold higher percentage than in the DLN, suggestive of local expansion of these cells. A higher percentage of NK cells were CD8-negative compared with DLN NK cells. AH cells specifically lysed allogeneic cells, and this cytotoxicity was mainly attributable to NK cells but not to CD4 or CD8 T lymphocytes. CONCLUSION: These results confirm the crucial role of CD4 cells in the allogeneic corneal graft rejection process and implicate NK cells as possible mediators of the rejection.

Factors influencing the decline in endothelial cell density after corneal allograft rejection.

PURPOSE: Corneal allograft rejection is one of the major causes of transplant failure. The purpose of the current study was to examine the decline in endothelial cell density (ECD) in patients experiencing allograft rejection, by comparing this decline with the normal evolution in patients who undergo penetrating keratoplasty (PKP) and to identify possible factors predictive of this endothelial cell loss after corneal allograft rejection. METHODS: In a case-control study of 45 corneas that underwent corneal allograft rejection, specular microscopy photographs taken within the shortest time preceding the onset of rejection and after the resolution of the rejection were analyzed. RESULTS: The observed percentage loss of ECD in 21 (47%) corneas was not significantly greater than expected. A second group of 13 (29%) corneas showed a decline in ECD that was significantly greater than expected. Finally there were 11 corneas (24%) in which endothelial cells were no longer observable. The only two risk factors that reached statistical significance after multiple logistic regression analysis were a delay in diagnosis (a delay of >1 day yielded an odds ratio of 10.40; P=0.02) and a recipient age of more than 60 years (odds ratio, 6.95; P=0.04). CONCLUSIONS: Corneal allograft rejection does not necessarily cause a higher than expected endothelial cell loss; almost half of the patients in this study showed a decline in ECD that is comparable to the decline in patients who undergo PKP and have an uneventful follow-up. The most important variable influencing the extent of endothelial cells loss is a delay in diagnosis and treatment.

Ocular bioerodible minitablets as strategy for the management of microbial keratitis.

PURPOSE: Evaluation in volunteers of ciprofloxacin-containing ocular gelling minitablets with prolonged release properties. METHODS: The irritation potential of ciprofloxacin-containing bioadhesive powder mixtures, used to prepare ocular bioerodible minitablets, was evaluated with a slug mucosal-irritation test. The tear pharmacokinetic profiles of ciprofloxacin were determined in six healthy volunteers after topical administration of a minitablet and a single eye drop in the lower fornix. The drug concentrations in the tear samples collected were measured by using a validated HPLC METHOD: Each volunteer was asked to give an evaluation of the preparations applied by answering a standard questionnaire. RESULTS: The results of the mucosal-irritation test demonstrated the nonirritating properties of the bioadhesive powder mixtures. The ocular minitablet, applied in the fornix was in general well tolerated by the healthy volunteers. The mean tear concentration of ciprofloxacin was 33.0, 135.2, and 33.7 microg/g at 30, 300, and 480 minutes after application of the minitablet. Mean tear levels of 84.7, 45.6, and 8.4 microg/g were obtained at 5, 30, and 60 minutes after application of an eye drop. CONCLUSIONS: Due to their prolonged drug release properties, the ocular minitablets containing ciprofloxacin can be considered as a promising drug delivery system to be used in the treatment of ulcerative bacterial keratitis.