Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

Epidemiological aspects of allergic conjunctivitis.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.

Japanese guidelines for allergic conjunctival diseases 2020.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease 2019. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases.

PURPOSE: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases. DESIGN: Open cohort study. PARTICIPANTS: Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791). METHODS: The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics. MAIN OUTCOME MEASURES: Changes in the corneal epitheliopathy score. RESULTS: Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus. CONCLUSIONS: The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.

Japanese guidelines for allergic conjunctival diseases 2017.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.

Blood level of tacrolimus in patients with severe allergic conjunctivitis treated by 0.1% tacrolimus ophthalmic suspension.

BACKGROUND: To estimate the efficacy and safety of 0.1% tacrolimus ophthalmic suspension based on the blood level of tacrolimus in patients with severe allergic conjunctivitis. METHODS: Fifty-two patients in whom topical anti-allergic agents had been ineffective were treated with 0.1% tacrolimus ophthalmic suspension twice daily for 12 weeks. Adverse drug reactions were monitored, as well as ocular symptoms and signs. The blood concentration of tacrolimus was measured before the initiation of treatment and 4 and 12 weeks later. RESULTS: About 75% of the patients without concomitant using of tacrolimus ointment had blood levels of tacrolimus below the detection limit of the assay (0.5ng/mL). On the other hand, 71% (week 4) and 57% (week 12) of patients with concomitant using of tacrolimus ointment had blood levels above the detection limit of the assay. However, the maximum blood concentration was less than 2ng/mL. Adverse drug reactions occurred in 16 patients. These were disorders of the eye such as warmness, irritation, and a burning sensation. However, all of the patients could continue treatment with tacrolimus for 12 weeks. There were no serious adverse events such as increased intraocular pressure or ocular infection during the study. All symptoms and signs improved over time. CONCLUSIONS: The good safety profile of 0.1% tacrolimus ophthalmic suspension based on the low blood concentration of tacrolimus, coupled with demonstrated efficacy, make it an important tool for treating severe allergic conjunctivitis.

[Evaluation of the efficacy of subjective symptoms, objective findings, and of a total tear IgE detection kit in diagnosis of allergic conjunctival diseases].

PURPOSE: To evaluate the efficacy of subjective symptoms, objective findings, and of a total tear IgE test kit in the diagnosis of allergic conjunctival diseases (ACD). SUBJECTS AND METHODS: The subjects were 223 patients with ACD, diagnosed according to the clinical practice guidelines for allergic conjunctival diseases in 28 medical facilities in Japan. The ACD patients were divided into the following five groups: 84 patients with seasonal allergic conjunctivitis (SAC), 52 patients with perennial allergic conjunctivitis (PAC), 41 patients with atopic keratoconjunctivitis (AKC), 38 patients with vernal keratoconjunctivitis (VKC) and 8 patients with giant papillary conjunctivitis (GPC). All cases were examined for clinical ACD, subjective symptoms, objective findings by the clinical score and by a total tear IgE test. An eosinophil examination by conjunctival smear was also performed in 87 ACD patients. RESULTS: The most prevalent subjective symptoms were itching (81.6%) and hyperemia (77.6%). The clinical scores of the objective findings in the patients with SAC, PAC, AKC, VKC and GPC were 16.3 +/- 3.8 (mean +/- SD) points, 16.2 +/- 2.8, 19.8 +/- 6.5, 23.1 +/- 5.3, and 21.4 +/- 3.9, respectively. In the total tear IgE test 72.2% of the ACD patients were positive; i.e., the ratios were 61.9% in SAC, 65.4% in PAC, 80.5% in AKC, 94.7% in VKC, and 75.0% in GPC. In the examination of eosinophils in the 87 ACD patients, 42.5% (37 eyes) were positive, i.e., the ratio was 20.0% in SAC, 36.8% in PAC, 53.3% in AKC, 75.0% in VKC and 33.3% in GPC. The rate of agreement between the total tear IgE test and the examination of eosinophils was kappa = 0.28 (Cohen kappa coefficient). CONCLUSION: Because of the high positive ratio in patients quasi-definitively diagnosed with ACD, we conclude that the total tear IgE test is useful as an auxiliary method for diagnosing ACD.

[A quality of life questionnaire for Japanese allergic conjunctival disease].

PURPOSE: To establish a specific quality of life (QOL) questionnaire for Japanese allergic conjunctival disease (ACD) (Japanese allergic conjunctival disease QOL questionnaire: JACQLQ). SUBJECTS AND METHODS: A multicenter study was conducted in 521 patients with ACD and 127 healthy volunteers (total 648 cases). The JACQLQ ver. 0 was developed by modifying the Japanese rhino-conjunctivitis QOL questionnaire (JRQLQ). The participants were asked to complete the questionnaire, and objective scores were determined by an ophthalmologist using a slit lamp. To confirm validity, item and factor analyses were conducted and correlation coefficients were calculated. RESULTS: The items were grouped into four subscales (Daily activity, Psychological well-being, Eye symptoms, Nasal symptoms) after factor analysis. The JACQLQ had good item-internal consistency (Cronbach's alpha: 0.846-0.934). QOL scores were correlated with eye itching, eye irritation and tearing. Objective scores were correlated with eye redness, eye itching and eye irritation. Face scores were correlated with eye itching, eye irritation and eye redness. CONCLUSION: The JACQLQ is a useful tool for assessing disease specific QOL in ACD.

Japanese guideline for allergic conjunctival diseases.

The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the above mentioned drugs.

[A prospective, observational, all-prescribed-patients study of cyclosporine 0.1% ophthalmic solution in the treatment of vernal keratoconjunctivitis].

PURPOSE: To evaluate the effectiveness and safety of topical cyclosporine 0.1% in patients with vernal keratoconjunctivitis (VKC). METHODS: All patients who were prescribed topical cyclosporine 0.1% during the 2 year period after market launch were registered and followed up for 6 months. We assessed the severity of 6 subjective ocular symptoms, such as itching and 10 objective signs, such as giant papillae in the tarsal conjunctiva. RESULTS: All scores for symptoms and signs in 2597 patients with VKC significantly decreased throughout a 6-month follow-up. For total symptoms scores, mean changes from baseline at 1, 3, and 6 months were -4.0, -4.8, and -5.1, respectively. Total sign scores were -4.6, -6.1, and -6.5, respectively. Thirty percent of topical steroid users were able to discontinue the steroids within 3 months. Adverse drug reactions (ADRs) were found in 7.44% of patients, the most common ADR being eye irritation. Ocular infections were observed in 1.44% of patients. During long-term use of topical cyclosporine 0.1%, there was no increase in the incidence of ADR and no late-onset ADRs. CONCLUSIONS: Topical cyclosporine 0.1% is an effective and safe treatment for VKC over the long term, provided care is exercised to avoid the occurrence of infection.

Reduced steroid-induced intraocular pressure elevation in tacrolimus-treated refractory allergic ocular diseases.

PURPOSE: To determine whether topical tacrolimus can lessen steroid-induced intraocular pressure (IOP) elevation. STUDY DESIGN: Open cohort post hoc analysis study. METHODS: Five hundred eleven patients with vernal keratoconjunctivitis or atopic keratoconjunctivitis (mean age 17.0 ± 9.2 years) were studied. All 511 patients were treated with topical tacrolimus with or without topical steroids, and the changes in IOP were measured monthly for 3 months. The elevation in IOP induced by use of topical steroids was calculated using mixed linear regression analyses. The relationship between the elevation in IOP within 4 weeks and the use or nonuse of tacrolimus reported in published data was analyzed using metaregression analysis to estimate the effects of tacrolimus on the IOP in eyes treated with topical steroids. RESULTS: The mean topical steroid-induced IOP elevation in tacrolimus-treated eyes was lower, by 5.2 mmHg (P = 0.04), than that in earlier published data without tacrolimus as the control. In the tacrolimus-treated eyes, the mean betamethasone-induced IOP elevation was 1.3 mmHg without discontinuation of the steroid. Metaregression analysis indicated that glaucoma history and younger age had significant effects on topical steroid-induced IOP elevation, by 4.0 mmHg (P = 0.002) and 3.9 mmHg (P = 0.01), respectively. In tacrolimus-treated eyes, the most significant effect on the IOP was associated with glaucoma history or medication; however, its effect on the IOP was limited to 1.7 mmHg elevation (P = 0.006). CONCLUSIONS: Topical tacrolimus may lessen the steroid-induced elevation in IOP in younger individuals and may be a good adjunctive therapy to avoid IOP elevation in refractory cases.

Effect of NIDEK optimized aspheric transition zone ablation profile on higher order aberrations during LASIK for myopia.

PURPOSE: To investigate the effect of the Optimized Aspheric Transition zone profile (OATz) that was devised to minimize the "red ring" in corneal topography on ocular higher order aberrations following LASIK for myopia. METHODS: Laser in situ keratomileusis with OATz using the Nidek Advanced Vision Excimer Laser Platform (NAVEX) was performed on 22 eyes with a 4.5-mm optical zone and 8.0-mm transition zone (OATz group). Conventional LASIK was performed on 11 eyes with a 6.0-mm optical zone and 7.0-mm transition zone as a control (conventional group). The higher order aberrations for the central 6-mm diameter were measured at 1 month postoperatively using a Hartmann-Shack wavefront sensor. In addition to the spherical aberration, the magnitude and orientation of trefoil, coma, tetrafoil, and secondary astigmatism were compared between two groups using Zernike vector analysis. RESULTS: The mean magnitude (root-mean-square) of the total higher order aberrations in the conventional group (0.70 +/- 0.28 microm) was significantly higher than that in the OATz group (0.51 +/- 0.15 microm, P < .05, unpaired t test). For spherical aberration, the OATz group had significantly lower values (0.22 +/- 0.17 microm) than the conventional group (0.38 +/- 0.23 pm, P < .05). The magnitude of coma in the conventional group was also higher than that in the OATz group (P < .05), and the mean axis of coma was 8.6 degrees in the conventional group and 64.3 degrees in the OATz group. No statistically significant differences were noted in the magnitude and axes of trefoil, tetrafoil, or secondary astigmatism between the two groups. CONCLUSIONS: The OATz profile may decrease the surgically induced increase of higher order aberrations, especially spherical aberration, following LASIK. However, a study with equivalent treatment groups and larger sample sizes is required for a definitive conclusion.

Comparison of myopic LASIK centered on the coaxially sighted corneal light reflex or line of sight.

PURPOSE: To compare refractive outcomes of myopic LASIK with centration on the coaxially sighted corneal light reflex (CSCLR) to centration on the center of the pupil (line of sight [LOS]). METHODS: The NIDEK CXIII excimer laser was used to treat 268 eyes with centration on the CSCLR (CSCLR group) and 288 eyes with centration on the LOS (LOS group). For the CSCLR group, the laser ablation was delivered 80% closer to the visual axis. One-month postoperative outcomes were compared. RESULTS: Preoperative manifest refraction spherical equivalent (MRSE) was -4.88+/-1.55 diopters (D) (range: -8.50 to -1.25 D) in the CSCLR group and -5.05+/-1.63 D (range: -9.75 to -1.50 D) in the LOS group. The postoperative MRSE was 0.17+/-0.39 D (range: -1.38 to -1.25 D) in the CSCLR group and 0.19+/-0.48 D (range: -1.63 to +1.88 D) in the LOS group. Safety (1.18) and efficacy (1.047) indices were statistically significantly higher in the CSCLR group compared to the LOS group (1.138 and 0.997, respectively) (P<.05). This trend was accentuated in a subgroup analysis of patients with >0.25-mm difference between the CSCLR and LOS, favoring the CSCLR group. A statistically significantly greater induction of higher order aberrations (P=.04) and coma (P<.01) was noted in the LOS group postoperatively. CONCLUSIONS: Myopic LASIK centered on the CSCLR was significantly safer and more effective than LASIK centered on the pupil (LOS), with significantly lower induction of coma and total higher order aberrations.

Air pollution significantly associated with severe ocular allergic inflammatory diseases.

Ambient air pollution is a well-recognized risk for various diseases including asthma and heart diseases. However, it remains unclear whether air pollution may also be a risk of ocular allergic diseases. Using a web-based, nation-wide, cross-sectional study design, we examined whether the level of ambient air pollution is significantly associated with the prevalence of ocular allergic diseases. A web-based questionnaire was posted to invite the participants who are members of the Japan Ophthalmologist Association and their family members. The answers from 3004 respondents were used to determine whether there were significant associations between the level of the pollutants and the prevalence of ocular allergic diseases. The study period was between March to May 2017. The data of the air pollutants during 2012 to 2016 were obtained from the National Institute for Environmental Studies. The prevalence of allergic diseases was calculated by post stratification and examined for significant associations with the level of pollutants using multiple logistic regression analyses. The prevalence of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC) in Japan was 45.4%, 14.0%, 5.3%, and 1.2%, respectively. The high prevalence of the severe forms of allergic conjunctivitis, including AKC and VKC, were significantly associated with the levels of the air pollutants. The prevalence of AKC was significantly associated with the levels of NO2 with an odds ratio (OR) of 1.23 (per quintile). The prevalence of VKC was significantly associated with the levels of NOx and PM10 with ORs of 1.72 and 1.54 respectively. The significant associations between the prevalence of AKC and VKC and the levels of air pollutants indicate that clinicians need to be aware that air pollutants may pose serious risks of vision threatening severe ocular allergy.

Topical Tacrolimus for Chronic Allergic Conjunctival Disease with and without Atopic Dermatitis.

Purpose/Aim: This study evaluated the efficacy of topical 0.1% tacrolimus ophthalmic suspension for treating chronic allergic conjunctival disease with and without atopic dermatitis. Materials and Methods: This study was conducted as a prospective observational post-market survey. Our large-scale study protocol was accepted by the Pharmaceuticals and Medical Devices Agency in Japan and included patients who were prescribed topical tacrolimus for the treatment of chronic allergic conjunctival disease from May 2008 to Aug 2010 in Japan. Topical tacrolimus was instilled 2 times daily for 6 months. The primary endpoint was the change from baseline in papillae-limbus-cornea clinical signs score (based on the presence of papillae, giant papillae, Trantas' dots, limbal swelling, and corneal epithelial signs). Remission rate following topical tacrolimus treatment was investigated using generalized estimating equations. Results: A total of 1821 subjects were included in the analyses. Six months into treatment, 83.0% and 87.7% of subjects with and without atopic dermatitis, respectively, were in remission (based on the papillae-limbus-cornea grading score). Topical tacrolimus treatment was equally effective in improving papillae-limbus-cornea grading scores from baseline in both study groups after 6 months of treatment. Additionally, the odds ratio for remission increased over time. The concomitant use of topical steroids improved papillae-limbus-cornea grading scores, including papillary signs with a statistically significant, but low odds ratio. Conclusion: Tacrolimus ophthalmic suspension is useful for treating chronic allergic conjunctival disease with and without atopic dermatitis. Clinical response to local tacrolimus therapy is dependent upon treatment duration.

The effect of a combined therapy with a histamine H1 antagonist and a chemical mediator release inhibitor on allergic conjunctivitis.

PURPOSE: To evaluate the efficacy of a combined therapy with levocabastine hydrochloride ophthalmic suspension and pemirolast potassium ophthalmic solution compared to single therapy with levocabastine hydrochloride ophthalmic suspension alone. METHODS: Thirty-two allergic conjunctivitis patients were randomized to combined-treatment (n = 15) or single-treatment groups (n = 17). The improvement of subjective symptoms as well as objective findings were evaluated. RESULTS: The degree of improvement was significantly higher in the combined-treatment group for lacrimation (p = 0.008) among the subjective symptoms, for conjunctival edema (p = 0.030), eyelid edema (p = 0.032) and conjunctival papilla formation(p = 0.040) among the objective findings. CONCLUSIONS: Both objective assessments and subjective symptoms of allergic conjunctivitis showed the greatest improvements when patients were treated with combined therapy as compared to single-agent therapy. The enhanced benefits of combined therapy may result from these agents having different mechanisms of action.

Incidence of intraoperative floppy iris syndrome in patients on either systemic or topical alpha(1)-adrenoceptor antagonist.

PURPOSE: To evaluate the incidence of Intraoperative Floppy Iris syndrome (IFIS) in relation to the usage of alpha(1)-adrenoceptor antagonists. DESIGN: Prospective, interventional case series. METHODS: In 2,643 consecutive eyes of 1,968 patients undergoing cataract surgery, occurrence of IFIS and use of alpha(1) antagonists were recorded. RESULTS: IFIS was observed in 29 eyes (1.1%) of 25 male patients, all of whom were receiving alpha(1) antagonists. In those receiving systemic tamsulosin, alpha(1A) selective antagonist, IFIS developed in 25 (43.1%) of 58 eyes. In those receiving systemic naftopidil, alpha(1A) and alpha(1D) antagonists, IFIS was found in 4 (19.0%) of 21 eyes. There was no case of IFIS in patients who received other systemic alpha(1) antagonists and in eyes treated with bunazosin eyedrops, a nonselective alpha(1) antagonist. CONCLUSIONS: IFIS occurred in 1.1% of cases treated with systemic alpha(1A)-adrenoceptor antagonists for benign prostatic hypertrophy. Topical nonselective alpha(1) antagonist did not induce IFIS.

Expression patterns of sialylated epitope recognized by KL-6 monoclonal antibody in ocular surface epithelium of normals and dry eye patients.

PURPOSE: To determine the association of the KL-6 epitope (sugar moiety) with MUC1 and its distribution on the ocular surface of human non-dry and dry eyes. METHODS: The human ocular surface was examined immunohistochemically and immunoelectron microscopically using monoclonal antibody (mAb) KL-6, which recognize a carbohydrate epitope of MUC1. The expression patterns of KL-6 epitope in corneal and conjunctival cells were examined by impression cytology from 24 non-dry eye volunteers and 43 dry-eye patients. RESULTS: In the cornea, bulbar conjunctiva, and limbus epithelium, mAb KL-6 reacted to the apical cell membrane of superficial cells and the intercellular space of superficial and wing cells. No immune reactivity of mAb KL-6 was observed in the basal plasma membrane of basal epithelial cells. Results of impression cytology indicated that the corneal epithelium of 13 of 24 non-dry eyes was weakly stained by mAb KL-6, whereas 42 of 43 dry eyes showed a mosaic pattern. In non-dry eyes, 19 of 24 bulbar conjunctival epithelia expressed the KL-6 epitope in a honeycomb pattern. In mild (17/19) and moderate (17/17) dry eye conjunctiva, the KL-6 epitope showed a mosaic pattern. However, the expression of KL-6 epitope decreased in severe dry eyes, showing a mosaic pattern in three of seven patients and labeling a few cells weakly in four of seven patients. CONCLUSIONS: These findings suggest that there is an upregulation of the sialylated KL-6 epitope of MUC1 by apical corneal and conjunctival cells in mild and moderate dry eyes. This upregulation may in part alleviate the consequences caused by goblet cell mucin dysfunction in dry eyes. It is noteworthy that the KL-6 epitope is downregulated in the conjunctiva of severe dry eyes, a phenomenon that may be explained in part by the malfunction of conjunctival epithelial cells.

Evaluation of the tear film stability after laser in situ keratomileusis using the tear film stability analysis system.

PURPOSE: To evaluate the tear film stability of patients before and after laser in situ keratomileusis (LASIK) using the tear film stability analysis system (TSAS). DESIGN: Prospective observational case series. METHODS: New videokeratography software for a topographic modeling system (TMS-2N) was developed that can automatically capture consecutive corneal surface images every second for 10 seconds. Thirty-four subjects (64 eyes) who underwent myopia LASIK were enrolled in this study. All subjects were examined with the new system before LASIK and at 1 week, 1 month, 3 months, and 6 months after the surgery. Corneal topographs were analyzed for tear breakup time (TMS breakup time) and breakup area (TMS breakup area). Based on pre-LASIK TSAS analysis, subjects were separated into normal and abnormal TSAS value groups. The criteria for the normal group were either TMS breakup time more than 5 seconds or TMS breakup area less than 0.2. The percentage of the occurrence of superficial punctuate keratitis was compared between the two groups with regard to subject's dry eye signs and symptoms. RESULTS: Tear film stability decreased significantly during the early period after LASIK, as indexed by decreased TMS breakup time and increased TMS breakup area. Tear film instability resolved at 6 months after surgery. Before LASIK, 22 subjects (43 eyes) had normal TSAS evaluation and 12 subjects (21 eyes) were abnormal. After LASIK, among normal TSAS value eyes, 8 of 43 (18.6%) eyes developed superficial punctuate keratitis. In sharp contrast, 14 of 21 (66.7%) eyes in the abnormal group displayed superficial punctuate keratitis, correlating well with the patients' dry eye symptoms. The difference in the presence of superficial punctuate keratitis after LASIK between normal and abnormal TSAS value groups was statistically significant (P <.001). Subjects with abnormal TSAS evaluation also displayed resistance to dry eye treatment and had extended period of recovery. CONCLUSIONS: Tear film stability analysis can be a useful means for screening LASIK candidates before surgery and for prognosticating dry eye symptoms thereafter.

Tear film stability analysis system: introducing a new application for videokeratography.

PURPOSE: To review our previous studies regarding the development of a tear stability analysis system (TSAS) using videokeratography and the clinical application of TSAS for evaluation of tear film stability in patients subject to laser in situ keratomileusis (LASIK). METHODS: New software, namely TSAS, was developed for the videokeratography system TMS-2N (topographic modeling system). TSAS automatically captures consecutive corneal surface images every second for 10 seconds. Corneal topographs were analyzed for tear breakup time (TMS-BUT) and tear breakup area (TMS-BUA, the ratio of breakup area to entire color-code area). First, we recruited volunteers to test the sensitivity and specificity of this new system in comparison with the routine method for tear stability analysis, tear film breakup time evaluation by slit-lamp microscope (SLE-BUT), with fluorescence staining. Second, we investigated the practicability of TSAS in dynamic evaluation of tear film stability before and after LASIK. RESULTS: TMS-BUT had a positive correlation with SLE-BUT, whereas TMS-BUA showed a negative correlation. Although they showed similar rates of specificity as SLE-BUT, the sensitivity rates of TMS-BUT and TMS-BUA were 97.5% and 95%, respectively, significantly higher than that of SLE-BUT (75%). The study on patients subject to LASIK showed that tear film stability significantly decreased during the early time period following LASIK and resolved at 6 months after surgery. Eyes that had abnormal TSAS evaluation tended to have higher risk of developing superficial punctuate keratitis and dry eye symptoms after LASIK, and their responses to treatment were slow. CONCLUSIONS: TSAS is a noninvasive and objective method with higher sensitivity for tear film stability analysis than SLE-BUT.