A beginner‘s guide to mucous membrane grafting for lid margin keratinization: Review of indications,surgical technique and clinical outcomes

The posterior lid margin, where the mucocutaneous junction (MCJ) between the eyelid skin and tarsal conjunctiva is located, plays a critical role in maintaining the homeostasis of the ocular surface. Posterior migration of the MCJ leads to lid-margin keratinization (LMK), which has a domino effect on the delicate balance of the ocular surface microenvironment. This occurs most commonly following Stevens-Johnson syndrome/toxic epidermal necrolysis and is not known to regress spontaneously or with medical therapy. Over time, LMK causes blink-related chronic inflammatory damage to the corneal surface which may have blinding consequences. Lid-margin mucous membrane grafting (MMG) is the only definitive therapy for LMK. Timely MMG can significantly alter the natural course of the disease and not only preserve but even improve vision in affected eyes. Literature searches were conducted on PubMed, using the keywords “mucous membrane grafts,” “lid margin keratinization,” “Stevens-Johnson syndrome,” “toxic epidermal necrolysis,” “lid related keratopathy,” and “lid wiper epitheliopathy”. This review, which is a blend of evidence and experience, attempts to describe the indications, timing, surgical technique, postoperative regimen, and clinical outcomes of MMG for LMK. The review also covers the possible complications and pearls on how they can be effectively managed, including how suboptimal cosmetic outcomes can be avoided. The authors hope that this review will aid ophthalmologists, including cornea and oculoplasty specialists, to learn and perform this vision-saving surgery better, with the aim of helping their patients with chronic ocular surface disorders, relieving their suffering, and improving their quality of life.     

Assessing the human lid margin epithelium using impression cytology

Purpose: To establish if impression cytology combined with histochemical and immunocytochemical staining can be used to assess epithelium of the human upper lid margin. Methods: Following an initial eye examination of 40 healthy subjects (19 soft contact lens wearers and 21 non‐contact lens wearers, aged 18–57 years), lid margin staining was assessed with lissamine green using slit lamp biomicroscopy and graded (grade 0–3). Impression cytology of the upper lid margin of both eyes was collected, fixed and stained with periodic acid Schiff (PAS) and haematoxylin for cell morphology analysis (Nelson grade) or for immunocytochemistry (keratinization‐related proteins: filaggrin, transglutaminase1 (TGase1) and cytokeratin 1/10). Results: In 57% of all subjects, grade 0 lissamine green staining showed a thin line (the Marx line), just posterior to the meibomian gland ducts. Grade 2 or 3 lissamine green staining was observed in 17% of all subjects. There was no difference between contact lens and non‐contact lens wearers for lid margin staining or Nelson grade (p = 0.4, Fisher’s exact test). PAS/haematoxylin staining and immunocytochemistry showed transition in epithelial cell morphology, with marginal conjunctival epithelium, mucocutaneous junction and squamous epithelium, adjacent to meibomian gland ducts. This transition in epithelium was associated with differential expression of keratinization‐related proteins (filaggrin, cytokeratin 1/10 and TGase1). Conclusion: Lid margin epithelium can be successfully sampled using impression cytology and further characterized using histochemistry and immunocytochemistry staining techniques. This approach can be applied to assess lid margin changes in conditions such as dry eye and meibomian gland dysfunction.     

Age-related morphological changes in lid margin and meibomian gland anatomy.

Meibomian gland dysfunction (MGD) is responsible for recurrent irritative symptoms. Attempts to characterize MGD have largely concentrated on microbial and lipid abnormalities in meibomian gland secretions. Few reports describe histological abnormalities in this disease, and fewer still morphological changes. This article follows a previous study that established a classification for MGD. This was based on morphological changes in the meibomian gland and lid margin. Using this classification, we studied the age-related changes in 80 subjects, between 5 and 87 years of age without ocular disease. The lid margin became thicker after childhood. Lid margin vascularity and cutaneous hyperkeratinization increased with age in both lids, whereas, telangiectasia increased with age in the lower lid and squamous blepharitis and posterior lid margin rounding were more common after 50 years of age in the upper lid. Multiple rows of meibomian gland orifices occurred more frequently in the upper than lower lid, and orifice narrowing and pouting increased with age. No age-related changes in the shape or form of the mucocutaneous function, gland ducts, or acini were found. Meibomian gland secretions were less easily expressed in the elderly. We have attempted to define a normal range of lid morphology in healthy children and adults that we believe to be important for the subsequent definition of lid disease, and in particular, posterior blepharitis.     

Episodic conjunctival inflammation after Stevens-Johnson syndrome

The authors studied the histopathologic, ultrastructural, and immunopathologic characteristics of conjunctiva from patients with Stevens-Johnson syndrome (SJS). A small subset of SJS patients with recurrent conjunctival inflammation unassociated with external factors such as lid margin keratinization, sicca syndrome, trichiasis, or entropion was identified. The ultrastructural and immunopathologic characteristics of the conjunctiva from these patients were distinctly different from those of the conjunctiva from SJS patients without recurrent conjunctivitis, and suggested an active, immunologically mediated inflammation. Vasculitis or perivasculitis, immunoreactant deposition in vessel walls, vascular basement membrane disruption, thickening, and reduplication, and a preponderance of helper T-lymphocytes, macrophages, and Langerhans' cells were the notable distinguishing features in those patients with recurrent conjunctival inflammation. This rare clinical syndrome may represent the ocular counterpart to recurrent dermal or oral mucosal erythema multiforme.     

In vivo confocal microscopy in blepharitis

BACKGROUND: Dysfunction of the meibomian glands with inflammation and obstruction has been suggested to be an important factor in the pathogenesis of chronic blepharitis. Few objective tests are, however, available to examine the meibomian glands directly. PATIENTS AND METHODS: Nineteen patients with anterior blepharitis, meibomitis, meibomian gland dysfunction or severe keratoconjunctivitis sicca associated with blepharitis as well as 10 patients with normal lid margins were examined with the HRTII/RCM in vivo confocal microscope. Scans of the tear film, the tarsal conjunctiva, the hair follicles and the meibomian glands were analysed by a masked observer. RESULTS: Patients with normal lid margins exhibited a minimal round cell infiltrate in the tarsal conjunctival epithelium and largely normal ducts of the meibomian glands lined with a multilayered epithelium as well as normal gland acini. In patients with anterior blepharitis, blepharitis associated with autoimmune peripheral ulcerative keratitis and blepharitis in the context of severe dry eye, confocal microscopy disclosed normal meibomian glands. In 12 patients with blepharitis/meibomitis or meibomian gland dysfunction, profound pathology was visible with dilatation and obstruction of the meibomian gland ducts. In 15 of 19 patients with blepharitis/meibomitis, but not in meibomian gland dysfunction, an intense inflammation was observed in the tarsal conjunctival epithelium and stroma. In one patient, demodex folliculorum was evident in vivo. In patients with normal lid margins as well as in patients with blepharitis, hair follicles appeared within normal limits. CONCLUSIONS: In vivo confocal microscopy allowed the examination of the tear film, the tarsal conjunctiva, the lid margin including the lash follicles and the meibomian glands. In patients with meibomian gland disease pathological changes could be visualised and documented objectively. The presence of an inflammatory infiltrate permitted us to differentiate between meibomitis and meibomian gland dysfunction. Changes of the lash follicles do not seem to play an important role in blepharitis. Thus, in vivo confocal microscopy represents an objective technique in the classification and follow-up of patients with blepharitis.     

Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?

PURPOSE: This study's purpose was to determine whether complete androgen insensitivity syndrome (CAIS) is associated with alterations in the meibomian gland and ocular surface. METHODS: Individuals with CAIS, as well as age-matched female and male controls, completed questionnaires which assessed dry eye symptoms and underwent slit lamp evaluations of the tear film, tear meniscus, lids and lid margins and conjunctiva. The quality of meibomian gland secretions was also analyzed. RESULTS: Our results demonstrate that CAIS is associated with meibomian gland alterations and a significant increase in dry eye signs and symptoms. Clinical assessment revealed that CAIS women, as compared to controls, had a significant increase in telangiectasia, keratinization, lid erythema and orifice metaplasia of the meibomian glands, and a significant decrease in the tear meniscus and quality of meibomian gland secretions. Questionnaire results showed that dry eye symptoms were increased over twofold in CAIS individuals, as compared to controls, including a significant increase in the sensations of dryness, pain and light sensitivity. CONCLUSION: Our results suggest that androgen insensitivity may promote meibomian gland dysfunction and an increase in the signs and symptoms of dry eye.     

Biogeography of the human ocular microbiota

PurposeThe human eye is composed of numerous microhabitats. The aim of this study was to understand the communality and differences in the microbiomes of various regions of the eye.MethodsFour ocular sites from different subject groups were assessed including the eyelid margin tissue from patients with lid abnormalities (n = 20), fornix and limbus conjunctival tissue from patients with pterygia (n = 23), ocular (conjunctival) surface swabs (n = 45) and facial skin swabs (n = 16). Microbial communities were analysed by extracting total DNA from samples and sequencing the 16S ribosomal(r)RNA gene using the Illumina MiSeq platform. Sequences were quality filtered, clustered into unique sequences (zOTUs) using the UNOISE pipeline in USEARCH and taxonomically classified using SILVA.ResultsA difference in bacterial richness and diversity was found between sites (P < 0.001) and for age (P < 0.035) but not for sex (P > 0.05). There was a difference in bacterial community structure and composition between sites (P < 0.001). Bacterial distribution could be broadly classified into three groups - zOTUs resident on the skin and lid margin but with low abundances at other sites (Corynebacterium, Staphylococcus), zOTUs found mainly on the ocular surface (Acinetobacter, Aeribacillus) and zOTUs mostly present in the conjunctiva and lid margin (Pseudomonas).ConclusionThe microhabitats of the human eye (ocular surface, conjunctiva, lid margin and skin) have a distinct bacterial biogeography with some bacteria shared between multiple regions while other bacteria occupy a more confined niche.     

Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders

PURPOSE: Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation. METHODS: We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK). RESULTS: Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC. CONCLUSION: The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.     

Staging of conjunctival squamous metaplasia by impression cytology

We modified the conventional impression cytology technique for conjunctival study by designing a 24-well Teflon sample holder, using cellulose acetate paper cut in an asymmetrical shape, and introducing Gill's modified Papanicolaou stain. Using this modified technique, we studied 35 normal subjects and 67 patients with various ocular surface disorders, 42 of whom were later found to have squamous metaplasia. Six different cytological stages were defined based on changes of goblet cell density, nucleus, and cytoplasm, encompassing three major steps: (1) loss of goblet cells, (2) increase of cellular stratification or enlargement of superficial cells, and (3) keratinization. This staging system allowed us to correlate pathological changes with clinical findings, and to investigate the action mechanism of squamous metaplasia of conjunctival epithelium. This modified impression cytology technique may help increase understanding of various ocular surface disorders.     

年龄相关性白内障患者睑板腺与眼表状况分析

背景 睑板腺是位于上下睑板内一种特殊分化的皮脂腺,其形态学和功能学的严重改变与多种眼表疾病有关,研究睑板腺形态学和功能变化与干眼的关系具有重要的临床意义. 目的 观察年龄相关性白内障患者的睑板腺形态、结构及功能变化,探讨衰老与睑板腺功能障碍(MGD)及眼表健康状态的关系.方法 采用系列病例观察研究方法,选取2016年3-9月在山西省眼科医院就诊的45岁以上年龄相关性白内障患者93例93眼作为研究对象,按照年龄将患者分为45～ 59岁组和≥60岁组;按照睑板腺缺失范围将受检眼分为睑板腺缺失范围≥1/3组和睑板腺缺失范围＜1/3组.采用裂隙灯显微镜检查眼表组织、睑缘形态、睑板腺开口形态和睑脂性状;采用眼表疾病指数(OSDI)量表问卷对眼表症状进行调查和评分;采用眼表综合分析仪测定受检眼泪膜破裂时间(BUT)、泪河高度、睑板腺缺失、结膜充血及角膜荧光素染色情况.结果 93例受检者均无干眼主观症状,OSDI问卷评分均＜12分.裂隙灯显微镜检查受检眼均未发现睑缘及皮肤黏膜交界线的形态学变化,无睑板腺开口、睑脂排出及睑脂性状的异常.眼表综合分析仪检查发现,42眼BUT缩短,占45.16％;52眼泪河高度下降,占55.91％;58眼睑板腺缺失范围≥1/3,占62.27％.45 ～59岁组受检眼睑板腺缺失评分为1.65±0.79,≥60岁组为1.86±0.72,差异无统计学意义(t=1.301,P=0.197).但相关分析示年龄与睑板腺缺失评分呈弱正相关(r5=0.323,P=0.002),与BUT及泪河高度均无明显相关性(r=0.154,P=0.141;r =-0.024,P=0.821);睑板腺缺失评分与BUT呈负相关(r3=-0.251,P=0.015),睑板腺缺失范围≥1/3组BUT异常的发生眼数明显多于缺失范围＜1/3组,差异有统计学意义(P=0.018). 结论 中老年人随着年龄的增长,睑板腺缺失逐渐加重;睑板腺缺失范围较大者发生泪膜不稳定的风险增加;早期MGD患者体征先于症状出现,临床工作中应重视无症状的MGD患者.     

提高对睑板腺功能障碍的认识 重视睑板腺功能障碍相关性干眼的药物治疗

睑板腺功能障碍（MGD）是临床常见的眼表疾病,以睑板腺终末导管的阻塞和／或睑板腺分泌物质或量的改变为特征,导致脂质向泪膜的排出减少,引起泪液蒸发过强。睑缘和睑板腺的炎症是引起睑板腺阻塞,进而导致MGD的直接原因,可引起眼表功能的异常。MGD的诊断主要依靠临床症状与体征,其症状与干眼的症状相似,因此无诊断特异性。体征主要包括睑缘形态的变化、睑板腺分泌异常和睑板腺缺失。MGD的治疗方法包括热敷、清洁睑缘、促进睑板腺的分泌、抗菌、抗炎治疗及润滑眼表,中度、重度MGD患者可给予必要的抗炎治疗,常用的抗炎药物有糖皮质激素、非甾体类抗炎药及免疫抑制剂。临床医师在进行眼部疾病的检查时应重视睑板腺的功能状态,尤其在角膜屈光手术及内眼手术前更应重视MGD的筛查,以免术后引起严重的眼表并发症,有效规避医疗风险。     

睑板腺功能障碍患者睑缘形态与睑板腺形态学的相关性研究

目的 研究睑板腺功能障碍（MGD）患者睑缘形态与睑板腺形态的相关性。设计 横断面研究。研究对象 2019年北京同仁医院行Lipiflow热脉冲治疗前的MGD患者30例（30眼）。方法 通过眼前节照相技术和Oculus眼表分析仪拍摄睑缘和睑板腺,并依据睑缘形态、睑板腺主体部形态、睑板腺开口和分泌物性状进行分类。睑缘形态分为肥厚、充血、角化和变形;睑板腺主体部形态分为缺失、白色节段、导管膨胀、萎缩、扭曲和分叉;睑板腺开口形态分为圆形、脂帽、脂塞和脂栓。依上述形态进行评分,运用Spearman相关分析研究睑缘形态与睑板腺形态的相关性。主要指标 睑缘及睑板腺形态评分,睑缘及睑板腺形态学相关系数（r）。结果 睑板腺开口形态与分泌物性状之间呈正相关（r=0.590,P=0.001）,睑板腺白色节段与睑板腺开口形态呈正相关（r=0.439,P=0.015）;睑板腺萎缩和分叉与睑板腺的分泌物性状呈负相关（r=-0.349,-0.374;P=0.048,0.042）。在睑缘形态中,睑缘角化的评分与睑缘形态总评分呈正相关,且相关关系最强（r=0.842,P＝0.000）;睑缘角化与睑板腺开口形态改变呈正相关（r=0.517,P=0.003）。在睑板腺形态中,睑板腺白色节段评分与睑板腺总评分呈正相关,且相关关系最强（r=0.535,P＝0.002）。结论 MGD患者睑缘形态与睑板腺形态部分存在相关关系。睑板腺白色节段作为睑板腺主体部的形态评估指标更为合理;睑缘角化作为睑缘的形态评估指标更为合理,且睑缘角化与睑板腺开口的形态改变相关。（眼科, 2020, 29： 355-360）     

Association between meibomian gland changes and aging, sex, or tear function

PURPOSE: To study changes in the lid margin and meibomian glands and their association with aging, sex, and tear function. METHODS: We examined 354 eyes in 177 subjects (76 men and 101 women; 21-93 years; mean age, 63.0 +/- 14.3 years) with no ocular symptoms or ocular surface disorders. Anatomic changes in the lid margin were studied using slit-lamp biomicroscopy. Meibomian gland function and morphology were evaluated on the basis of meibum expression and meibography, respectively. Tear function and ocular surface epithelium were assessed with the Schirmer test, by tear film break-up time, and with a fluorescein staining test. RESULTS: Eyes with abnormal lid margin anatomy, hyposecretion of meibum, and meibomian gland dropout were seen in 26 (7.3%), 46 (12.4%), and 68 eyes (18.6%), respectively, with a significant association between each finding and aging (P = <0.0001, 0.0498, and <0.0001, respectively). In patients < or =69 years of age, no significant association was found between meibomian gland-related findings and sex. However, a high incidence of abnormal lid margin and gland dropout was noted in men > or =70 years of age compared with women. No significant association was found between changes in the lid margin and meibomian glands and tear function in patients > or =40 years of age. CONCLUSION: Among symptom-free subjects, we found that changes in the lid margin and meibomian glands were closely related to aging. Among elderly subjects, changes in the anatomic lid margin and meibomian gland morphology were observed more frequently in men than in women. Tear function showed no association with either changes in the lid margin or function of the meibomian glands.     

眼睑刷区域的解剖及组织形态的共聚焦显微镜观察

目的应用共聚焦显微镜对眼睑刷区域进行实时、活体观察,了解该区域的解剖和组织形态,为临床进一步诊断和治疗眼睑刷上皮病变及早期干眼提供依据。方法系列病例研究。选择2013年9月至2014年3月于北京积水潭医院眼科就诊的患者共20例（20眼）。其中无眼睑刷上皮病变者5例;眼睑刷上皮病变程度为中至重度者15例,应用共聚焦显微镜对其眼睑刷附近区域进行观察,采集图片,并进行分析。结果眼睑刷区域上皮为类似于结膜的立方上皮,与睑缘处的复层鳞状上皮不同,并在睑板腺开口处有明显的分界线。眼睑刷区域上皮包含白细胞及杯状细胞。相比无眼睑刷上皮病变者,眼睑刷上皮病变为中至重度者的眼睑刷区域可观察到更多的孔洞和裂隙。结论眼睑刷区域的解剖、组织形态及病理改变可以通过共聚焦显微镜进行活体、无创、实时、清晰的观察,其结果可为研究眼睑刷病变机理以及临床上诊断和治疗眼睑刷上皮病变及早期干眼提供依据。     

【In Press】Cinical efficacy of combined topical 0.05% cyclosporin A and 0.1% sodium hyaluronate in the dry eyes with meibomian gland dysfunction

AIM: To investigate the efficacy of combined topical 0.05% cyclosporin A (CsA, Restasis®, Allergan pharmaceuticals, USA) and 0.1% sodium hyaluronate treatment in dry eyes with meibomian gland dysfunction. METHODS: In this retrospective analysis, 53 patients (106 eyes) with meibomian gland dysfunction (MGD) were enrolled and performed lid warm massage for 10min daily and be instilled preservative free sodium hyaluronate 0.1% eye drops 4 times daily. Patients were divided into subjects treated with topical 0.05% cyclosporine A and preservative free sodium hyaluronate vehicle (CsA group, n=74 eyes) and subjects treated with the preservative free sodium hyaluronate vehicle (control group, n=32 eyes). They were evaluated at baseline and at 1, 2, and 3mo for subjective symptoms and objective signs including tear break-up time, schirmer test, corneal staining score, lid margin telangiectasia, meibomian gland secretion, and conjunctival injection. RESULTS: In the short-term treatment, CsA group showed a statistically significant improvement in the ocular surface disease index (P<0.001), tear film break-up time (P=0.004), schirmer test score (P=0.008) and lid margin telangiectasia (P=0.021) by repeated measure ANOVA. Additionally, mean changes from baseline in ocular surface disease index (P<0.001), tear film breakup time (P=0.001), schirmer test score (P=0.029), corneal staining score (P=0.047), eyelid margin telangiectasia (P=0.002), conjunctival injection (P=0.030) were improved better in CsA group than in the control group at 3mo. However, there was no significant difference between the two groups in meibomian gland secretion (P=0.67). CONCLUSIONS: In dry eyes with meibomian gland dysfunction, 0.05% cyclosporin A improves the tear film stability as well as subjective ocular discomfort, and is effective in controlling lid margin inflammation.     

Oral erythromycin treatment for childhood blepharokeratitis

Blepharokeratitis is a chronic external ocular and adnexal inflammatory condition marked by erythematous and edematous lid margins, lid margin crusting and scaling, meibomian gland inflammation and inspissation, and conjunctival hyperemia. The associated keratitis usually involves the inferior cornea and is characterized by punctate epithelial keratopathy and marginal stromal infiltrates. The inflammation sometimes leads to corneal thinning, scarring, and vascularization. The standard therapy for adult blepharokeratitis includes lid hygiene, topical cortico-steroid preparations, and topical antibiotics. Oral tetracycline and its analogues, doxycycline and minocycline, are used in adults to treat associated meibomian gland dysfunction. Whereas blepharitis is common in children, blepharokeratitis is rare and is often associated with severe ocular and psychosocial morbidity. Treatment of youths may be problematic because of poor compliance with lid hygiene and therapy that includes drops and ointment.(1) Furthermore, the use of tetracycline and its analogues is contraindicated in children aged less than 8 years because it may cause dental enamel abnormalities. Isolated case reports have suggested that erythromycin may be a reasonable alternative to tetracycline in childhood blepharokeratitis.(2,3) We report on the successful treatment of this condition with oral erythromycin in 5 children.     

Efficacy of commercially available topical cyclosporine A 0.05% in the treatment of meibomian gland dysfunction

OBJECTIVE: To investigate the efficacy of topical cyclosporine A 0.05% (tCsA) (Restasis, Allergan Pharmaceuticals) in the treatment of meibomian gland dysfunction (posterior blepharitis). METHODS: Thirty-three patients with symptomatic meibomian gland dysfunction were randomized in a prospective study to either tCsA or placebo (Refresh Plus preservative-free artificial tears), 2 times daily for 3 months. They were evaluated at baseline and at 1, 2, and 3 months for subjective symptoms and objective signs including meibomian gland inclusions, lid margin vascular injection, tarsal telangiectasis, fluorescein staining, tear breakup time, and Schirmer scores. RESULTS: Twenty-six patients completed the study. All patients were tested for ocular symptoms, lid margin vascularity, tarsal telangiectasis, meibomian gland inclusions, tear breakup time, and fluorescein staining. At the 3-month visit, the tCsA group showed a greater improvement in ocular symptoms than the placebo group, but this difference was not statistically significant. At the 3-month visit, several objective examination findings were statistically significantly (P < 0.05) improved in the tCsA group compared with the placebo group. These differences included lid margin vascular injection, tarsal telangiectasis, and fluorescein staining. The most significant finding (P = 0.001) was the greater decrease in the number of meibomian gland inclusions in the tCsA group compared with the placebo group. CONCLUSIONS: Topical CsA may be helpful in the treatment of meibomian gland dysfunction (posterior blepharitis). Topical CsA did not induce an improvement in the symptoms, but it did decrease the number of meibomian gland inclusions in patients with meibomian gland dysfunction.     

Management of the late ocular sequelae of Stevens-Johnson syndrome

The acute conjunctivitis seen initially in Stevens-Johnson syndrome is followed by a cicatricial phase, which often leads to severe ocular surface disease and visual morbidity. Manifestations include keratinization of the conjunctiva, lid margins, and lacrimal and meibomian ducts, resulting in an unstable tear film and mechanical trauma to the conjunctiva and cornea with blinking. Limbal stem cell deficiency is the most vision-threatening sequela of Stevens-Johnson syndrome, as it causes corneal neovascularization, chronic corneal inflammation, and an irregular corneal epithelium. Management of late sequelae often requires a multipronged approach, including strategies for ocular surface protection, ocular surface support, and ocular surface reconstruction. In this review, established therapies, as well as new experimental therapies, are discussed.     

In vivo findings of the bulbar/palpebral conjunctiva and presumed meibomian glands by laser scanning confocal microscopy

OBJECTIVE: To report in vivo laser scanning confocal microscopic findings of the normal human conjunctiva and presumed meibomian glands and to investigate the potential application of this confocal microscope (HRT II Rostock Cornea Module) as a diagnostic device for normal and abnormal ocular surface structures. METHOD: Four healthy volunteers (51-, 49-, 31-, and 30-year-old men) participated in this study. The temporal bulbar conjunctiva, approximately 5 mm away from the limbus, and the upper tarsus conjunctiva of each patient were examined in vivo by a laser confocal microscope. Also, presumed meibomian glands beneath the tarsal conjunctiva were examined. RESULTS: In all subjects, the in vivo laser confocal microscope obtained similar images. In the superficial epithelial cell layer of the bulbar conjunctiva, numerous bright nuclei were observed. We also observed many Langerhans cells with characteristic dendritic morphology and goblet cells with relatively homogeneous brightness in the bulbar conjunctiva. Most interestingly, the palpebral conjunctival epithelium with invaginations or crypts was observed. In addition, weblike structures, presumably meibomian glands, were observed beneath the palpebral conjunctival epithelium. CONCLUSIONS: These results indicate that in vivo laser confocal microscopy can be used not only to visualize the bulbar conjunctiva but the upper tarsus conjunctiva and possibly subconjunctival meibomian glands. Further investigations of conjunctival and meibomian gland pathologies may further elucidate the potential of this device in clinical ophthalmology.