Topical 0.005% tacrolimus eye drop for refractory vernal keratoconjunctivitis

Purpose

To evaluate the efficacy and safety of topical 0.005% tacrolimus eye drop for treatment of refractory vernal keratoconjunctivitis (VKC).

Methods

This prospective study included 20 eyes of 10 patients with refractory VKC, who had active symptomatic disease despite conventional medications including topical steroids. After discontinuing all other medications, patients were treated with topical 0.005% tacrolimus eye drop four times a day. Changes in subjective symptoms and objective signs after treatment were evaluated, and development of possible complications was assessed.

Results

Mean age of patients was 21.3±7.4 years and mean duration of VKC was 12.1±5.8 years. After starting tacrolimus eye drop, patients were followed for a mean duration of 10.7±3.7 months (range, 6–15 months). All symptoms including itching, redness, photosensitivity, foreign body sensation, and mucus discharge improved after the treatment; itching was the first symptom to show dramatic relief. In addition, there was improvement in objective signs including conjunctival hyperaemia, conjunctival papillary hypertrophy, giant papillae, limbal hypertrophy, corneal punctate epithelial erosions, and corneal pannus; conjunctival hyperaemia was the first sign to show improvement. No patient required addition of other medications including steroids for further relief. Any attempt to discontinue tacrolimus eye drop was associated with recurrence of patients'' symptoms and signs, necessitating continued use of the medication during the entire follow-up time. No ocular complication related to tacrolimus was noted.

Conclusion

Topical 0.005% tacrolimus eye drop seemed to be a safe and effective treatment for steroid-resistant refractory VKC; however, long-term use was needed to control the disease.     

儿童春季卡他性角结膜炎与干眼症相关性分析

目的:探讨春季卡他性角结膜炎患儿的泪膜功能,并分析其与儿童干眼症发生的相关性。方法:取临床诊断为春季卡他性角结膜炎的86例患儿作为观察组,取年龄与之匹配的正常儿童86例作为对照组,分别做基础泪液分泌试验(schirmer Itest)、泪膜破裂时间(BUT)、角膜荧光素(FL)染色检查。结果:儿童春季卡他性角结膜炎常合并干眼症的相关症状:瞬目次数增加(33%),干涩感(14%),烧灼感(10%)。观察组泪膜功能相关检查:双眼泪液分泌试验均低于对照组(P=0.01),双眼泪膜破裂时间短于对照组(P<0.01),双眼角膜荧光素染色评分高于对照组(P<0.01)。泪膜功能改变与疾病严重程度有关,与病程、亚型分类无关。结论:春季卡他性角结膜炎患儿泪膜功能发生改变,是干眼症的易患人群。     

Treatment of vernal keratoconjunctivitis a double-masked study

Thirty-one children aged five to 14 years with severe vernal keratoconjunctivitis (VKC) were enrolled in a double-masked study evaluating the efficacy of three ophthalmic preparations: cromolyn sodium (Opticrom) 2%, artificial tears and fluorometholone 0.1% (FML). These drugs were coded respectively as A, B, C, and dispensed in similar bottles. Both eyes were treated, and drug assignment was made at random.

Objective assessment of the disease activity was done under slit lamp by two ophthalmologists according to a five-point scale. The results were tabulated and the chi-square test performed. Decoding of the drugs was done only after completion of the statistical analysis. FML was found effective with a statistically significant difference from the other two drugs, both after the first week on the initially assigned treatment (p = 0.05) and on completion of the treatment period according to protocol (p = 0.005). Although several patients improved under cromolyn sodium, there was no statistically significant difference between cromolyn sodium 2% and artificial tears. All the preparations were well tolerated. One patient developed bilateral allergic blepharitis when treated with FML during the study. Another patient who responded well to FML developed posterior subcapsular cataract while continuing treatment with corticosteroids a few months after completion of the study.     

不同浓度氟米龙滴眼液治疗儿童重度混合型春季角结膜炎

目的：观察不同浓度氟米龙滴眼液治疗儿童重度混合型春季角结膜炎的临床效果。

方法：选取2022-03/09于我院门诊就诊的重度混合型春季角结膜炎儿童患者50例100眼,随机分为两组,A组患者25例50眼给予0.1%氟米龙滴眼液联合0.05%环孢素滴眼液(Ⅱ)治疗; B组患者25例50眼给予0.02%氟米龙滴眼液联合0.05%环孢素滴眼液(Ⅱ)治疗。治疗1mo,观察两组患者SPEED问卷评分及角膜荧光素染色(FL)评分、泪膜破裂时间(TBUT)、泪液分泌试验(SⅠt)、眼红分析、非侵入式泪河高度(NIKTMH)、角膜光密度等眼部参数,记录不良反应发生情况。

结果：治疗1mo,两组患者SPEED评分、FL评分及眼红分析结果均有显著差异(均P<0.05),TBUT、SⅠt及NIKTMH结果均无差异(均P>0.05),但角膜不同深度、不同直径范围角膜光密度具有差异性(均P<0.05)。治疗1mo,两组患者眼压无显著差异(16.21±2.90mmHg vs 16.05±2.75mmHg,P>0.05),且治疗过程中均未出现明显不良反应。

结论： 0.1%氟米龙滴眼液可有效治疗儿童重度混合型春季角结膜炎,效果优于0.02%氟米龙滴眼液。     

盐酸西替利嗪联合普拉洛芬治疗儿童春季角结膜炎的疗效及依从性

目的：观察盐酸西替利嗪滴剂联合普拉洛芬滴眼液治疗儿童春季角结膜炎的疗效及依从性。
　　方法：收集2014-01/2015-12到我院眼科门诊就诊,诊断为双眼春季角结膜炎的63例儿童患者,按照随机数字表法将患儿分为试验组和对照组,试验组给予盐酸西替利嗪滴剂联合1g/L普拉洛芬滴眼液进行治疗,盐酸西替利嗪滴剂2次/d,每次5滴(0.25mL,2.5mg,≤6岁)或每次10滴(0.5mL,5mg,>6岁),直接口服或加入饮料食物中服用;1 g/L普拉洛芬滴眼液4次/d ,1滴/次,点眼;对照组仅给予盐酸西替利嗪滴剂进行治疗,2次/d,每次5滴(0.25mL,2.5mg,≤6岁)或每次10滴(0.5mL,5mg,>6岁),直接口服或加入饮料食物中服用。疗程共14 d。记录患儿用药前后的症状和体征、用药依从性和药物不良反应情况,并对用药前后的症状及体征进行评分并比较。
　　结果：两组患儿治疗后的症状、体征及总体评分均有明显改善,差异有统计学意义( t试验组症状=10.41, P<0.05;t试验组体征=10.05,P<0.05;t试验组总体=10.75,P<0.05;t对照组症状=8.11,P<0.05;t对照组体征=8.89,P<0.05;t对照组总体=8.41,P<0.05);试验组治疗后症状、体征和总体评分低于对照组,差异有统计学意义(t症状=5.27,P<0.05;t体征=3.97,P<0.05;t总体=4.32,P<0.05);试验组有效率(85%)显著高于对照组有效率(60%),差异有统计学意义(χ2=4.92,P<0.05);94%的患儿依从性良好;未见患儿出现困倦及口干等不良反应。
　　结论：盐酸西替利嗪滴剂联合普拉洛芬滴眼液对于治疗儿童春季角结膜炎具有显著疗效及良好的依从性,明显提高治疗的有效率,且无明显不良反应,安全性高。     

Occurrence of vernal keratoconjunctivitis in children infected with human immunodeficiency virus

Purpose:To study the occurrence of vernal keratoconjunctivitis (VKC) as an ocular manifestation of human immunodeficiency virus (HIV) in pediatric patients.Methods:A retrospective study was done on the observations of cases of HIV-positive children. All seropositive patients from the Anti-Retroviral Therapy clinic were referred to the department of ophthalmology for evaluation. Retrospective correlation of CD4 count with active cases of VKC was done. All patients underwent a comprehensive ophthalmic evaluation including visual acuity, slit lamp and dilated fundus examination.Results:A total of 72 children were included, 70 males and 2 females. Of these, 63 (87.5%) had VKC, three (4.2%) had cataract, two (2.8%) had cytomegalovirus retinitis retinitis, and four (5.5%) had no ophthalmic findings.Conclusion:There is a an evident association of HIV, VKC cases, and reduced CD4 count. More research is required on this topic.     

核因子-κB在春季角结膜炎的表达

目的 研究核转录因子(nuclear factor kappa B,NF-κB)在春季角结膜炎(vernal keratoconjunctivitis,VKC)中的表达,探讨VKC的发病机制.方法 设实验组和对照组实验组为VKC结膜组,共6例,对照组为正常结膜组,共4例.取VKC眼术中切下增生的结膜组织及角巩膜缘处病变的球结膜组织,和角膜移植术中健康供体眼近角巩膜缘处的正常球结膜组织,运用免疫组织化学及免疫印迹法分别检测VKC患者病变结膜组织和正常结膜组织中NF-κB的表达情况.结果 在正常结膜组织中仅少量NF-κB表达,而VKC病变结膜组织中NF-κB的表达明显增高,后者的表达量约为前者的1.5倍,差异具有统计学意义(P＜0.05).结论 NF-κB可能参与VKC的发病机制.     

Efficacy of topical cyclosporin A 0.05% in conjunctival impression cytology specimens and clinical findings of severe vernal keratoconjunctivitis in children

Purpose  To evaluate the efficacy of topical cyclosporin A 0.05% in managing the symptoms of severe vernal keratoconjunctivitis (VKC). Methods  Fifty-four children with severe VKC were included in this study. All 54 patients were treated with topical cyclosporin A (CsA) 0.05% for 3 months. Ocular signs and symptoms were scored in all patients at entry and after 3 months. Conjunctival impression cytology specimens were examined on the day of enrollment and at the end of the treatment period. Results  The mean scores for severity of signs and symptoms significantly decreased after 3 months compared with those at entry (P < 0.001). The density of inflammatory cells in the conjunctival impression cytology specimens decreased significantly. No side effects of the treatment with CsA 0.05% eyedrops were observed. Conclusions  Topical CsA 0.05% eyedrops were found to be safe and effective in the treatment of patients with VKC. Consistent with these results, topical CsA may efficiently reduce conjunctival inflammation in severe VKC.     

他克莫司治疗春季卡他性角结膜炎的疗效分析

目的：评价免疫抑制剂——他克莫司滴眼液治疗春季卡他性角结膜炎(vernal keratoconjunctivitis,VKC)的治疗效果。

方法：随机双盲试验,安慰剂对照。收集四川大学华西医院眼科16例门诊患者,将16例患者按就诊顺序随机分为治疗组与对照组。治疗组使用他克莫司滴眼液,对照组使用他克莫司滴眼液基础液,观察期为28d。对研究眼眼部体征和自觉症状分别进行单项评分,以治疗前后眼部体征总分变化量为主要疗效指标,主观症状为次要疗效指标。

结果：(1)组内比较：两组症状和体征在用药前后的差异具有统计学意义,治疗组用药后各个时期的自觉症状评分均低于用药前,且随着时间推移,症状评分逐渐降低,差异有统计学意义,对照组用药后不同时期之间的差异无统计学意义。(2)组间比较：两组患者的主观症状和体征在用药前和用药后第一次复查时差异无统计学意义,之后两次复查差异均具有统计学意义。评分变化量(用药前评分-用药后评分)在用药后第一次复查时差异无统计学意义,之后两次复查差异均具有统计学意义。

结论：他克莫司滴眼液能改善VKC患者的体征与症状,对于使用抗过敏滴眼液无明显改善的VKC,具有迅速、优良的改善效果,可应用于临床。     

Topical 2% cyclosporine A in preservative-free artificial tears for the treatment of vernal keratoconjunctivitis

BACKGROUND: A double-masked, placebo-controlled trial to evaluate the short-term efficacy and safety of topical 2% cyclosporine A in preservative-free artificial tears for patients with vernal keratoconjunctivitis. METHODS: Twenty patients with severe vernal keratoconjunctivitis were included in the study. All were treated with topical 2% cyclosporine A eye drops. One eye of each patient was administered 2% cyclosporine A in preservative-free artificial tears; the fellow eye received the placebo (vehicle) for the first 2 weeks, in a double-masked, placebo-controlled trial. Thereafter, the placebo eye received cyclosporine A (open trial). Symptoms and signs were scored on the day of enrollment and at the end of week 2, 4, and 14. RESULTS: At the end of week 2, no statistically significant decrease was noted from baseline in mean scores of either signs (p = 0.18) or symptoms (p = 0.50) in the eyes that received placebo. On the other hand, a statistically significant decrease was observed in both sign and symptom scores (p < 0.001, for both) of eyes that received cyclosporine A. Significant differences were also noted at 2 weeks in mean scores of both signs and symptoms (p < 0.001, for both) between the eyes that received cyclosporine A and those that received placebo. At week 4 and 14, statistically significant decreases in both sign scores and symptom scores were noted compared with baseline in the eyes that received cyclosporine A and in the eyes that had initially received placebo (p < 0.001, for all). INTERPRETATION: Topical 2% cyclosporine A in preservative-free artificial tears is effective in alleviating signs and symptoms of patients with severe vernal keratoconjunctivitis and had no observed side effects over the course of the study.     

Clinical profile of medicolegal cases presenting to the eye casualty in a tertiary care center in India

Purpose:The purpose of this study was to analyze the clinical profile of medicolegal cases (MLCs) presenting to the eye casualty in a tertiary care hospital.Results:Out of 188 MLCs, 164 (87.2%) were male. Mean age (±standard deviation) was 31.6 (±12.7) years. Age ranged from 7 to 75 years. Twenty-six (13.8%) patients had bilateral involvement. The fist was the most common mode of injury, which was seen in 109 (58%) cases. A total of 27 (14.3%) patients had associated extraocular injury. No evidence of ocular or orbital trauma (malingering) could be found in 13 (7%) patients. Mechanical trauma was present in 169 (90%) patients with injury to globe in 129 (69%) patients and injury to lid or orbit without damage to the globe in 40 (21%) patients. Chemical injury was observed in 6 (3%) patients. Closed globe injury (CGI) was seen in 116 eyes and open globe injury (OGI) was noted in 29 eyes. The most common type of injury, zone, pupil, and grade of injury in CGI were Type A or contusion (79%), Zone I (72%), Pupil B (absence of relative afferent pupillary defect) in 95%, and Grade A [visual acuity (VA) ≥20/40] in 68% of the eyes, respectively. The most common type of injury, zone, pupil, and grade of injury in OGI were Type B or penetrating (48%), Zone II (38%), Pupil B (59%), and Grade D (VA 4/200-light perception) (42%), respectively.Conclusions:The most common form and mode of ocular injury in MLC were closed globe injury and fist, respectively. The most common type of injury in CGI and OGI was contusion and penetrating injury, respectively.     

春季角结膜炎发生圆锥角膜的机制研究进展

春季角结膜炎是一种好发于儿童及青少年,以反复发作的慢性炎症为主要表现的过敏性眼表疾病,容易出现角膜并发症如圆锥角膜。圆锥角膜是一种以角膜局部圆锥样突起为主要特征的角膜病变。既往研究分别提出了春季角结膜炎及圆锥角膜的发病机制及前者进展为后者的危险因素,但具体机制尚不明确。回顾文献发现二者有共同的发生机制及类似的细胞因子表达,包括Ⅰ型及Ⅳ型超敏反应、炎症反应、酶学变化、氧化应激、机械性损伤等方面。文章旨在概述春季角结膜炎发生圆锥角膜的机制及可能涉及的细胞因子,以期为春季角结膜炎发生圆锥角膜的预防和临床诊疗策略提供参考。     

Etiology and clinical profile of childhood optic nerve atrophy at a tertiary eye care center in South India

Background:Optic nerve atrophy is an important ophthalmological sign that may be associated with serious systemic conditions having a significant bearing on the overall morbidity of the child. Studies specific to etiology of childhood optic atrophy are scarce, this being the first such study from India to the best of our knowledge.Aim:The aim was to analyze the clinical features and etiology of diagnosed cases of optic nerve atrophy in children <16 years of age.Results:A total of 324 children (583 eyes) were identified. Among these 160 (49%) presented with defective vision, 71 (22%) with strabismus, 18 (6%) with only nystagmus. Rest had a combination of two or three of the above symptoms. Sixty-five patients (20%) had a unilateral affection. Hypoxic ischemic encephalopathy seen in 133 patients (41%) was the most frequent cause of childhood optic atrophy, followed by idiopathic in 98 (30%), hydrocephalus in 24 (7%), compressive etiology in 18 (5%), infective in 19 (6%), congenital in 6 (2%), inflammatory in 5 (2%) patients, respectively.Conclusion:Hypoxic ischemic encephalopathy appears to be the most common cause of optic atrophy in children in this series. The most common presenting complaint was defective vision.     

Clinical,histological and immunohistochemistry characteristics of cornea in the sequelae stage of chronic vernal keratoconjunctivitis

Purpose:To report the clinical outcomes and histopathological and immunohistochemistry (IHC) features in eyes with the sequelae stage of vernal keratoconjunctivitis (VKC).Methods:Investigative study of corneal samples obtained following surgical intervention for vision restoration in four eyes of three patients with VKC. Patient 1 (an 11-year-old boy) had deep anterior lamellar keratoplasty in both eyes, Patient 2 (a 24-year-old male) underwent superficial keratectomy followed by penetrating keratoplasty, and Patient 3 (a 22-year-old male) underwent penetrating keratoplasty. The corneal samples retrieved after surgical intervention were assessed for histology features and immunohistochemistry (IHC) studies.Results:The grafts were clear till the follow-up of 2–18 months. Histopathology of all four corneal samples showed epithelial hyperplasia, absent Bowman layer, thick hyalinized stromal lamellae, vascularization, and chronic inflammatory cells such as lymphocytes and plasma cells. IHC showed strong expression of CK 3 in both eyes of Patient 1 and no expression in Patients 2 and 3. The marker for limbal stem cells, ABCG2, was absent in all four samples; however, p63α was expressed strongly in Patients 2 and 3, moderately in the right eye of Patient 1, and marginally expressed in the left eye of Patient 1.Conclusion:The eyes in the sequelae stage of VKC (having corneal scarring and 360° hypertrophied limbus) can be managed favorably with keratoplasty and amniotic membrane transplantation without allogenic/cadaveric stem cell transplantation. The expression of transient progenitor cells in the scarred corneas of VKC patients in the sequelae stage suggests that the limbal stem cell dysfunction is more likely partial and self-renewal of limbal stem cells is a plausibility in these eyes.     

Effectiveness of a modified therapeutic protocol for the management of vernal keratoconjunctivitis based on Bonini’s graded clinical severity

Purpose:To evaluate the effectiveness of a modified therapeutic protocol used for vernal keratoconjunctivitis (VKC) based on severity as per Bonini grading system.Methods: This was a prospective observational clinical study conducted with 123 eyes of 63 patients. A meticulous clinical examination was performed, and data was documented in all the cases. Patients on known systemic atopy and antiallergic therapy were excluded from the study. Eyes with a clinical diagnosis of VKC were segregated based on Bonnini’s grading system. A treatment protocol was created depending on the grade of VKC. Therapeutic responses were documented at 3 weeks, 3 months, 6 months, 12 months, and 24 months. Grading of the eyes was performed in each visit.Results: The mean age of the patients was 8.85 years with a standard deviation of 4.48 years. Males were predominant, and 95.24% had bilateral manifestation. The palpebral component was the most common form of manifestation. Itching was the most common manifestation, followed by congestion, discharge, and papillae in a decreasing order. Also, 68% of patients were in grade 2, 14% in grade 3, 12% in grade 1, and the rest were in grade 4. Following the treatment protocol, 70% showed signs of significant improvement in grade by the end of 6 weeks, reaching 90% at the end of 6 months (P = 0.074) and 92% at the end of 12 months (P = 0.002). Also, 52.4% versus 77.8% of patients had no recurrence in the pre- versus posttreatment protocol and it was statistically significant (P = 0.001).Conclusion: Grading of VKC gives a clear evaluation of the severity and progression of the condition. Besides, significant improvement in the grades was observed with fewer incidences of recurrences following execution of the therapeutic protocol. Hence, it is essential to maintain a treatment protocol in our clinical practice to provide grade-based therapy and monitor accurate changes in the clinical condition.     

Efficacy of nedocromil 2% versus fluorometholone 0.1%: a randomised, double masked trial comparing the effects on severe vernal keratoconjunctivitis

AIMS: To compare the efficacy of topical nedocromil 2% with fluorometholone 0.1% in vernal keratoconjunctivitis (VKC). METHODS: In a double masked random design, 24 patients with severe vernal keratoconjunctivitis were placed at random on nedocromil 2% eye drops in one eye and fluorometholone 0.1% in the fellow eye. At the end of the 2 week treatment period, the patient crossed over the eye drops (if asymptomatic in one eye), or continued with nedocromil sodium in both eyes (if asymptomatic in both eyes). All patients were examined weekly and ocular surface temperature recorded for a period of 6 weeks. RESULTS: Improvement in the watering, discharge, conjunctival hyperaemia, papillary hypertrophy, and Trantas' dots was noted in both groups, but overall fluorometholone was significantly more effective than nedocromil. Eyes treated with fluorometholone showed a significant decrease in ocular surface temperature compared with nedocromil treated eyes (p = 0.03). CONCLUSIONS: Both nedocromil and fluorometholone were effective in ameliorating the signs and symptoms of vernal keratoconjunctivitis. No adverse effects were noted in the nedocromil group.     

In vivo confocal microscopy of meibomian glands and palpebral conjunctiva in vernal keratoconjunctivitis

Purpose:

To investigate the correlations between conjunctival inflammatory status and meibomian gland (MG) morphology in vernal keratoconjunctivitis (VKC) patients by using in vivo confocal microscopy (CM).

Materials and Methods:

Nineteen VKC patients (7 limbal, 7 tarsal, and 5 mixed forms) and 16 normal volunteers (controls) were enrolled. All subjects underwent CM scanning to obtain the images of upper palpebral conjunctiva and MGs. Inflammatory cell (IC) density in palpebral conjunctival epithelial and stromal layers, Langerhans cell (LC) density at lid margins and the stroma adjacent to the MG, and MG acinar unit density (MGAUD) were recorded. The longest and shortest diameters of MG acinar were measured. The Kruskal-Wallis test was used to compare the parameter differences whereas the Spearman''s rank correlation analysis was applied to determine their correlations.

Results:

Among all groups, no significant statistical differences were found in epithelial and stromal IC densities, mean values of MG acinar unit densities, or longest and shortest diameters. Both LC parameters in the tarsal-mixed groups were significantly higher than those in the limbal and control groups. All LC densities of VKC patients showed a positive correlation with MGAUD and shortest diameter.

Conclusions:

In VKC patients, the conjunctival inflammatory status could be associated with the MG status. In vivo CM is a noninvasive, efficient tool in the assessment of MG status and ocular surface.     

Keratoglobus: An experience at a tertiary eye care center in India

Context:

This study was carried out as a part of an internal audit and is the largest series of patients having keratoglobus, published in the literature. Poor visual acuity of the patients indicates the blinding nature of the disease.

Aims:

We report our experience with patients having keratoglobus at a tertiary eye care center in India.

Settings and Design:

Retrospective study.

Materials and Methods:

We analyzed adults and pediatric patients (<16 years) with keratoglobus, seen during 2008–2012. The age, gender, consanguinity, presenting ocular signs, ocular and systemic associations, visual acuity, corneal topography, and surgeries were documented.

Results:

Forty-eight patients (mean age 22 ± 15 years, 31 males) having keratoglobus were analyzed. 21 patients (42 eyes) were <16 years. Twelve eyes (16 events) had positive history of trauma. The presenting clinical signs were corneal scars/scars of tear repair (15 eyes), hydrops, healed and acute (14 eyes) and corneal or globe rupture (9 eyes). Best-corrected visual acuity was >20/40 in 6/42 (14.3%) pediatric eyes and 15/53 (28.30%) adults. Visual acuity ranging from counting of fingers to no light perception was noted in 20/53 (37.74%) adults and 21/42 (50%) pediatric patients; 13/20 (65%) with blue sclera and 8/22 eyes (36.37%) without blue sclera. Vernal keratoconjunctivitis was present in one pediatric patient. Choroidal osteoma, retinitis pigmentosa, and retinal detachment were present in adults. Surgeries performed were corneal tear repair (5 eyes), tissue adhesive application (2 eyes), descematopexy (4 eyes) and penetrating keratoplasty (PK - 8 eyes: Three had post-PK glaucoma, graft failure-one eye, 4 patients wore scleral lens - prosthetic replacement of the ocular surface ecosystem).

Conclusions:

About 50% of pediatric eyes (65% having blue sclera) had no functional vision. Trivial trauma was responsible for corneal rupture indicating need for protective glasses. About 50% patients had post-PK glaucoma though grafts were clear.