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Lacrimal and meibomian glands contribute to the aqueous and lipid components of tear film, respectively. Their evaluation remains central to diagnosing and managing dry eye disease (DED). The review discusses the differences and reliability of various diagnostic tests and commercially available devices used for DED diagnosis. Slit-lamp-based techniques are direct palpebral lobe and tear flow assessment, Schirmer test, meibum quality and expressibility, and evaluation of tear meniscus height. Non-invasive tear meniscus height (TMH), tear break-up time (TBUT), lipid layer thickness (LLT), and meibography are machine-based diagnostic tests. The structure–function correlation of the tear-producing glands gives more comprehensive details than either information alone. Many devices are available in the market, which make DED diagnosis an easy feat, but the tests should be interpreted keeping in mind the intra-observer and inter-observer repeatability. Also, the tear film displays a huge variability as per the environmental conditions and impact of blinking. Hence, the examiner should be well versed with the techniques and repeat the test two to three times to obtain an average reading, which is more reliable. The recommended sequence of tests for diagnosing DED is a dry eye questionnaire, TMH, LLT, NIBUT (FBUT if non-invasive test is unavailable but should be performed after osmolarity), tear osmolarity, meibography, and ocular surface staining. Invasive tests such as Schirmer should be performed after the non-invasive tear film diagnostic testing.

Bilateral corneal blindness with severe dry eye disease (DED), total limbal stem cell deficiency with underlying corneal stromal scarring and vascularization, combined with adnexal complications secondary to chronic cicatrizing conjunctivitis is a highly complex situation to treat. In such eyes, procedures such as penetrating keratoplasty alone or combined with limbal stem cell transplantation are doomed to fail. In these eyes, keratoprosthesis (Kpro) or an artificial cornea is the most viable option, eliminating corneal blindness even in eyes with autoimmune disorders such as Stevens–Johnson syndrome, ocular mucous membrane pemphigoid, Sjogren's syndrome, and nonautoimmune disorders such as chemical/thermal ocular burns, all of which are complex pathologies. Performing a Kpro in these eyes also eliminates the need for systemic immunosuppression and may provide relatively early visual recovery. In such eyes, the donor cornea around the central cylinder of the Kpro needs to be covered with a second layer of protection to avoid desiccation and progressive stromal melt of the underlying cornea, which is a common complication in eyes with severe DED. In this review, we will focus on Kpro designs that have been developed to survive in eyes with the hostile environment of severe DED. Their outcomes in such eyes will be discussed.

Purpose: To understand the bacterial microbiome changes associated with Sjogren's syndrome (SS) and non-Sjogren's syndrome (NSS) aqueous-deficient dry eyes compared to healthy eyes. Methods: Bacterial microbiome was generated from the deoxyribonucleic acid of tear film samples in healthy (n = 33), SS (n = 17), and NSS (n = 28) individuals. Sequencing of the V3-V4 region of the 16S rRNA gene was performed on the Illumina HiSeq2500 platform. Quantitative Insights Into Microbial Ecology (QIIME) pipeline was used to assign taxa to sequences. Statistical analysis was performed in R to assess the alpha diversity and beta diversity indices. Significant changes between the healthy, SS, and NSS cohorts were depicted by principal coordinate analysis (PCoA), differential abundance, and network analysis. Results: Tear microbiome was generated in healthy, SS, and NSS samples. Phyla Actinobacteria, Firmicutes, and Bacteroidetes showed significant changes in SS and NSS compared to healthy. Genera Lactobacillus and Bacillus were predominantly present in all samples. PCoA and heat map analysis showed distinct clusters for SS and NSS from the healthy cohort. Genera Prevotella, Coriobacteriaceae UCG-003, Enterococcus, Streptomyces, Rhodobacter, Ezakiella, and Microbacterium significantly increased in abundance in SS and NSS compared to a healthy cohort. Bacteria–bacteria interaction in SS, NSS, and healthy cohorts was predicted by CoNet network analysis. This analysis predicted a major hub of interaction for the pro-inflammatory bacterium Prevotella in the SS and NSS cohorts. Conclusion: The results of the study indicate significant changes in the phyla and genera in SS and NSS compared to healthy. Both discriminative analysis and network analysis indicated a possible association of predominant pro-inflammatory bacteria with SS and NSS.

Dry eye disease (DED) is an emerging global health concern with meibomian gland dysfunction (MGD) being the most common subtype of DED. Despite being quite prevalent, the pathophysiological mechanisms governing MGD are poorly understood. Animal models for MGD can be a valuable resource to advance our understanding of this entity and explore novel diagnostic and therapeutic modalities. Although a lot of literature on rodent MGD models exists, a comprehensive review on rabbit animal models is lacking. Rabbits offer a great advantage over other animals as models for studying both DED and MGD. Rabbits have a widely exposed ocular surface and meibomian gland anatomy comparable with humans, which makes performing dry eye diagnostic tests possible using clinically validated imaging platforms. The existing MGD models in rabbits can broadly be classified as pharmacologically induced and surgically induced models. Most models show keratinization of the meibomian gland orifice with plugging as the final common pathway for developing MGD. Thus, understanding the advantages and disadvantages of each rabbit MGD model can help researchers choose the appropriate experimental plan based on the objective of the study. In this review, we discuss the comparative anatomy of the meibomian glands in humans and rabbits, various rabbit models of MGD, translational applications, unmet needs, and future directions in developing MGD models in rabbits.

Evaporative dry eye (EDE) due to meibomian gland dysfunction (MGD) is one of the common clinical problems encountered in ophthalmology. It is a major cause of dry eye disease (DED) and of ocular morbidity. In EDE, inadequate quantity or quality of lipids produced by the meibomian glands leads to faster evaporation of the preocular tear film and symptoms and signs of DED. Although the diagnosis is made using a combination of clinical features and special diagnostic test results, the management of the disease might be challenging as it is often difficult to distinguish EDE from other subtypes of DED. This is critical because the approach to the treatment of DED is guided by identifying the underlying subtype and cause. The traditional treatment of MGD consists of warm compresses, lid massage, and improving lid hygiene, all measures aimed at relieving glandular obstruction and facilitating meibum outflow. In recent years, newer diagnostic imaging modalities and therapies for EDE like vectored thermal pulsation and intense pulsed light therapy have emerged. However, the multitude of management options may confuse the treating ophthalmologist, and a customized rather than a generalized approach is necessary for these patients. This review aims to provide a simplified approach to diagnose EDE due to MGD and to individualize treatment for each patient. The review also emphasizes the role of lifestyle modifications and appropriate counseling so that patients can have realistic expectations and enjoy a better quality of life.

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.

Purpose: To describe the features enabling the identification of the orientation of Descemet stripping automated endothelial keratoplasty (DSAEK) lenticule with the assistance of vital dyes. Methods: This is a blinded experimental lab-based study, including 30 microkeratome prepared precut DSAEK lenticules. The lenticules were divided into control and study arms which included 10 unstained and 20 stained lenticules, respectively. In the study arm, vital dyes like trypan blue (TB), brilliant blue (BB), indocyanine green (ICG) and fluorescein stain (FS) were used to stain 5 lenticules each. They were examined by experienced (group 1) and novice surgeons (group 2) to identify the correct orientation of the lenticule. The results were tabulated and analyzed. Results: Of the 30 lenticules examined, the average of total scores obtained by each observer was higher (78%) in group 1 as compared to group 2 (65.3%) which was statistically significant (P < 0.005). In group 1, the accuracy of identifying the correct orientation of unstained lenticules was 70% which improved to 82% on staining. The accuracy in group 2 was 58% with unstained lenticules which improved to 69% on staining. Within the study arm, irrespective of surgical experience, the accuracy was highest with BB (86%), followed by TB (82%), ICG (72%) and FS (62%). Conclusion: This study found that the accuracy of identifying the orientation of DSAEK lenticules increased with experience and with the assistance of staining using vital dyes. This accuracy improved with blue dyes like brilliant blue and trypan blue, irrespective of the level of experience.

Ocular involvement in cases of bullous pemphigoid is rare and when present, the signs are usually subtle and in the form of fine tarsal scarring and dry eye disease. The current report aims to describe the clinical features and management protocols in a series of cases with aggressive ocular manifestations at presentation. All cases of bullous pemphigoid seen between 2017 and 2020 were included in this retrospective case series. Data regarding the clinical features, treatment administered, and outcomes was collected. Five cases (n=10 eyes) of bullous pemphigoid disease with ocular involvement were included. All eyes had significant cicatricial conjunctival changes in the form of symblephara, inferior forniceal shortening, and tarsal conjunctival scarring. Conjunctival granulomas were present in 3/10 eyes. Corneal involvement in the form of punctate keratitis was present in all eyes while 4/10 eyes had an epithelial defect as well. The management of these cases involved topical therapy with corticosteroids and lubricants (n=10 eyes) while pulse doses of intravenous methyl prednisolone were administered in 5/5 cases. Pulse intravenous cyclophosphamide was supplemented in 2/5 cases. Adequate control of the disease was noted in 3/5 cases while one case had a recalcitrant form of the disease and developed a dermalised ocular surface in both eyes. The last patient was lost to follow up during the course of therapy. Bullous pemphigoid can present with an aggressive form of cicatrizing conjunctivitis similar to other variants of autoimmune blistering disorders and must be considered as a differential in cases presenting with ocular cicatricial disease. Long-term intensive immunosuppression is required for the management of these cases to preserve the visual function and the integrity of the globe.

Ocular involvement in cases of bullous pemphigoid is rare and when present, the signs are usually subtle and in the form of fine tarsal scarring and dry eye disease. The current report aims to describe the clinical features and management protocols in a series of cases with aggressive ocular manifestations at presentation. All cases of bullous pemphigoid seen between 2017 and 2020 were included in this retrospective case series. Data regarding the clinical features, treatment administered, and outcomes was collected. Five cases (n=10 eyes) of bullous pemphigoid disease with ocular involvement were included. All eyes had significant cicatricial conjunctival changes in the form of symblephara, inferior forniceal shortening, and tarsal conjunctival scarring. Conjunctival granulomas were present in 3/10 eyes. Corneal involvement in the form of punctate keratitis was present in all eyes while 4/10 eyes had an epithelial defect as well. The management of these cases involved topical therapy with corticosteroids and lubricants (n=10 eyes) while pulse doses of intravenous methyl prednisolone were administered in 5/5 cases. Pulse intravenous cyclophosphamide was supplemented in 2/5 cases. Adequate control of the disease was noted in 3/5 cases while one case had a recalcitrant form of the disease and developed a dermalised ocular surface in both eyes. The last patient was lost to follow up during the course of therapy. Bullous pemphigoid can present with an aggressive form of cicatrizing conjunctivitis similar to other variants of autoimmune blistering disorders and must be considered as a differential in cases presenting with ocular cicatricial disease. Long-term intensive immunosuppression is required for the management of these cases to preserve the visual function and the integrity of the globe.

This study aimed to identify the anterior segment high-resolution optical coherence tomography (HR-OCT) and HR-OCT angiography (HR-OCTA) features suggestive of limbal stem cell deficiency (LSCD) as confirmed by both impression cytology (IC) and in vivo confocal microscopy (IVCM). This was a single-centre prospective cross-sectional study including 24 eyes of 22 patients with clinical suspicion of LSCD based on peripheral superficial corneal vascularisation and scarring. On IC and IVCM, performed and interpreted by blinded observers, 12 eyes each were diagnosed with and without LSCD. Additionally, 10 eyes of 5 healthy volunteers with no ocular pathology were also imaged. The 136 HR-OCT/A images of these 34 eyes were analysed with respect to 12 imaging parameters; the parameters most suggestive of LSCD were identified and the sensitivity and specificity were calculated. In the LSCD group, the most common aetiology was ocular chemical burns (83%), whereas in the non-LSCD group, the most common aetiology was viral keratitis (67%). Multiple logistic regression analysis revealed that mean epithelial reflectivity, mean stromal reflectivity, and mean superficial vascular density were the parameters that were diagnostic of LSCD on HR-OCT/A (p < 0.0001). A ratio of the mean epithelial reflectivity to stromal reflectivity of >1.29 corresponded with a high sensitivity (91.7%) and specificity (98.75%); while a mean superficial vascular density score of >0.38 corresponded with a sensitivity of 97.9% and specificity of 73.8%. In conclusion, HR-OCT/A as a non-invasive imaging modality could prove to be a useful tool for confirming the diagnosis of LSCD, with potential clinical and research applications.