Lid Margin Microbiome in Stevens-Johnson Syndrome Patients With Lid Margin Keratinization and Severe Dry Eye Disease.

Purpose: The current study evaluated the lid margin microbiome of keratinized lid margins of patients with chronic Stevens-Johnson syndrome (SJS) and compared it with healthy controls and historically reported lid margin microbiome of patients with meibomian gland dysfunction (MGD). Methods: Eyelid margin swabs of 20 asymptomatic adults (mean age = 29 ± 12 years) and 10 patients with chronic SJS (mean age = 31.2 ± 14 years) with lid margin keratinization were sequenced using next generation of 16S rDNA V3 to V4 variable region. Within SJS, the keratinized lid margin microbiome was compared with adjacent eyelid skin. Results: All patients had obstructive MGD, and mean Schirmer I value was 2.8 ± 1.9 mm. The phyla were similar in two groups, whereas at the genera level, an increase in the relative abundance of Corynebacterium, Haemophilus, Azotobacter, and Afipia and a decrease of Acinetobacter was noted in SJS compared to healthy lid margins. SJS-associated microbiota displayed lesser diversity and more heterogeneity than healthy controls. The Principal Components Analysis (PCA) plot revealed wide separation in the SJS and the control groups. Correlational network analysis revealed Corynebacterium and Sphingomonas forming a major hub of negative interactions with other bacterial genera in the SJS group. Significant differences exist in the prevalent genera between keratinized lid margins and historically reported meibum microbiome of patients with MGD. In addition, the eyelid skin of patients with SJS had predominant Staphylococcus, whereas Corynebacterium and Pseudomonas were more in the keratinized lid margins compared to the eyelid skin microbiome. Conclusions: Lid margin microbiome is significantly altered in the keratinized lid margins of patients with SJS compared to the eyelid skin of patients with SJS, normal lid margins, and patients with MGD.

Secondary bacterial corneal infection caused by Myroides species in primary fungal keratitis.

A middle-aged male patient presented with a central corneal perforation in a deep stromal infiltrate in his left eye. An emergency therapeutic penetrating keratoplasty was performed. Microbiological evaluation of the corneal scraping specimen revealed septate fungal filaments on stains. However, culture reports after 24 hours from the scraping sample and the excised half corneal button showed growth of gram-negative bacilli. This pathogen was identified as an aerobic, non-fermentative, gram-negative, bacillus by conventional microbiology and confirmed as Myroides species by the VITEK 2 Compact system (bioMérieux, Marcy l'Etoile, France). Susceptibility to chloramphenicol was noted based on which the patient was treated with topical chloramphenicol 0.5%. No recurrence of the infection was noted. This is the first reported case of corneal infection with the Myroides species of bacteria which, heretofore, have been known to cause endocarditis and urinary tract infections.

Multiple conjunctival autografts from the contralateral eye for management of recurrent symblepharon in eyes with unilateral chemical burn.

We present two cases which underwent complex ocular surface reconstruction to achieve a stable ocular surface. Conjunctival autograft (CAG) procedure was required more than once, in addition to simple limbal epithelial transplantation to address extensive symblepharon in the eyes with total unilateral limbal stem cell deficiency secondary to acid ocular burns. These cases demonstrate that multiple CAGs may be harvested from the contralateral unaffected eye to correct recurrent symblepharon without any donor site complications if the correct surgical technique is adopted.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Long-term outcomes of glued (sutureless) amniotic membrane transplantation in acute Stevens-Johnson syndrome/toxic epidermal necrolysis: a comparative study.

PURPOSE: To compare the effectiveness and efficiency of a glued (sutureless) technique for amniotic membrane transplantation (AMT) with a traditional sutured one in the setting of acute Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: This retrospective cohort study evaluated all patients diagnosed with SJS/TEN between 2008 and 2020 within our hospital network who received AMT in the acute phase according to our protocol and had at least one ophthalmic follow-up in the chronic phase. Primary outcomes included best-corrected visual acuity (BCVA) at the most recent visit, presence of a severe ocular complication (SOC) via predefined criteria, time to procedure and duration of procedure. Random effects model analysis was used to evaluate the impact of potential covariates on outcome measures. RESULTS: A total of 23 patients (45 eyes) were included: 14 patients (27 eyes) in the AMT suture group and 9 patients (18 eyes) in the AMT glue group. There was no difference between the two groups in BCVA at the most recent visit (p=0.5112) or development of a SOC (p=1.000). The glue method was shorter in duration than the suture method (p<0.001). Random effects model additionally indicated that there was no difference in BCVA at most recent follow-up between patients who had received glued versus sutured AMT (p=0.1460). CONCLUSIONS: Our glued technique for AMT is as effective as our sutured technique in stabilising the ocular surface and mitigating chronic ocular complications in SJS/TEN. The glued technique is also shorter in duration and performed more expediently than the sutured technique.

Clinical profile and management of ocular superglue injuries: Case series and review of literature.

PURPOSE: To describe the clinical profile and management of patients with ocular superglue injury (OSI). METHODS: This retrospective study included all patients with OSI who presented at a tertiary eye care institute between 2016 and 2020. Data regarding demographics, clinical profile, and management were collected. RESULTS: A total of 66 eyes of 58 patients (24 children, 34 adults) with a median age of 22.5 years [interquartile range (IQR): 11.3-31] were included. All cases sustained accidental injuries, with domestic injury at home being the most common location of injury among children (79%) and adults (53%) ( P = 0.39). The median visual acuity at presentation was worse in children [0.3 logMAR (IQR: 0.2-0.4)] as compared to adults [0.1 logMAR (IQR: 0.1-0.3)] ( P = 0.03)]. The most common clinical sign at presentation was conjunctival congestion in 77% of eyes (51/66) followed by polymerized glue stuck to the eyelashes and eyelids in 52% of eyes (34/66). The median duration from the time of injury to presentation was 2 hours in both groups. All eyes resolved with medical management. Examination under anesthesia was required in three children (13%) to evaluate the extent of OSI. None of the patients had long-term ocular complications. CONCLUSION: Improper and careless handling of superglue in the domestic setting may cause accidental ocular injuries that require immediate medical attention. OSI represents less severe ocular injuries that respond to medical therapy alone and is not associated with long-term visual morbidity. Modifications in the packaging of superglue containers and awareness about their deleterious effects could prevent these injuries.

Pseudopithomyces Maydicus and Phialophora Chinensis Rare Fungal Keratitis: Case Series, DNA Sequencing, Antifungal Susceptibility Patterns.

PURPOSE: We report two cases of fungal keratitis due to rare melanized fungal pathogens in ocular infection, one is the first case report of keratitis due to Pseudopithomyces maydicus and the second is keratitis due to rare fungal pathogen in ocular infections Phialophora chinensis. METHOD: Conventional mycology during routine diagnostics helped in identifying these rare fungal isolates, following which we proceeded for the confirmation of identification by DNA sequencing and did in-vitro antifungal susceptibility test to understand their susceptibility pattern. The clinical information for these two patients were collected from hospital electronic medical records. RESULTS: We discuss the clinical presentation, treatment given, and clinical outcome in these patients and correlate these with the conventional microbiology and sequencing techniques, which helped in identifying the pathogen and the in-vitro antifungal susceptibility of these rare isolates. We also do a brief literature review for these two rare fungal pathogens. CONCLUSIONS: Pseudopithomyces maydicus and Phialophora chinensis are rare causes of fungal keratitis due to melanized fungi. Both of this fungal keratitis respond well to medical therapy alone if diagnosed and treated early.

Direct Immunofluorescence Findings and Factors Affecting Conjunctival Biopsy Positivity in Ocular Mucous Membrane Pemphigoid.

PURPOSE: The aim of this study was to describe the direct immunofluorescence (DIF) findings and factors affecting conjunctival biopsy positivity in patients clinically diagnosed with ocular mucous membrane pemphigoid (OMMP). METHODS: This retrospective observational case series included patients with clinical OMMP who underwent conjunctival biopsy for DIF in at least 1 eye between 2018 and 2021 in an institutional setting. The primary outcome measures were association of age and chronic ocular complications with biopsy positivity. RESULTS: Of 61 patients, DIF positivity was seen in 33 (54.1%) clinically suspected cases of OMMP. Of 39 patients who underwent bilateral biopsy, 23 (59%) were positive, of which 12 (52%) were positive in both eyes while 11 (48%) were positive in 1 eye. Of 22 patients who underwent unilateral biopsy, 10 (45%) were positive. Of the 100 biopsied eyes, 45 (45%) were DIF positive. Among the immunoreactants studied, linear deposition of C3 was seen in all 45 positive eyes (100%). Increasing age was significantly associated with higher likelihood of biopsy negativity ( P = 0.032), whereas a greater Sotozono chronic ocular complication score, indicative of disease severity, was associated with low likelihood of biopsy positivity ( P = 0.0042) and lower overall expression of immunoreactants on DIF ( P = 0.0007). CONCLUSIONS: Older patients and patients with more severe ocular surface disease sequelae are likely to have negative DIF results. To optimize the chances of confirming the diagnosis of OMMP by DIF, both eyes should be biopsied early in the disease course. If 1 eye is being biopsied, the less affected eye must be chosen.

Ocular surface pseudoepitheliomatous hyperplasia secondary to allergic eye disease: clinical features and management.

PURPOSE: To study the clinical characteristics and treatment outcomes of ocular surface pseudoepitheliomatous hyperplasia (PEH) associated with chronic vernal keratoconjunctivitis (VKC). METHODS: This retrospective study includes 39 eyes of 32 patients with VKC induced PEH who presented from 2016-2022. A database search was conducted for diagnosis of PEH, and data on clinical features, imaging characteristics, and treatment were analyzed. RESULTS: Of the 32 patients, 11 (34%) were children and adolescents, 21 (66%) were adults. PEH was common in males (72%) and ocular surface squamous neoplasia (OSSN) was the commonest referral diagnosis (43.7%). Mean age at presentation was 26.62 ± 10.18 (range: 6-52) years. While history of VKC was present in 21 patients, 11 were diagnosed with VKC at the time of diagnosis of PEH. The mean base/largest diameter was 5.2 ± 1.67 mm. Anterior segment optical coherence tomography (AS-OCT) showed irregular hyper-reflective epithelium, epithelial dipping, and sub-epithelial hyper-reflective lesion with shadowing in all lesions. Of the 31 eyes that received medical therapy, 21 (67%) and 10 (32%) eyes showed complete and partial resolution respectively with median time to resolution of 3(IQR:2-4) months. Eight eyes that underwent surgical excision showed complete resolution and one developed partial limbal stem cell deficiency. CONCLUSION: Ocular surface PEH is a manifestation of chronic VKC which closely mimics OSSN. Detailed history-taking, examination for signs of allergy, and AS-OCT imaging can distinguish it from OSSN. It responds well to medical therapy and should be considered first-line therapy before planning any surgical intervention.

Impact of Symblepharon Management With Ocular Surface Reconstruction on Scleral Lens Fitting in Eyes With Chronic Cicatrizing Conjunctivitis and Keratopathy.

PURPOSE: The aim of this study was to describe the importance of symblepharon release with ocular surface reconstruction (OSR) for optimal fitting of scleral contact lenses (SCLs) in eyes with chronic cicatrizing conjunctivitis (CCC) and keratopathy. METHODS: This retrospective study included 32 eyes with CCC and keratopathy with symblepharon which underwent symblepharon release with OSR and were fitted with SCLs. The primary outcome measure was the improvement in best-corrected visual acuity with SCL wear. RESULTS: A total of 32 eyes of 29 patients (66% men) with a median age of 30.5 years were included. The common causes of CCC were Stevens-Johnson syndrome (66%) and ocular burns (16%). The most common location of symblepharon was superior (59%) with limbal involvement in most eyes (94%). Symblepharon release was combined with mucous membrane grafting (63%), amniotic membrane grafting (31%), or conjunctival autografting (6%). The median interval between symblepharon release with OSR and SCL trial was 15 weeks [interquartile range (IQR): 6-24]. The median best-corrected visual acuity improved from logMAR 1.5 (IQR: 1.2-1.8) to logMAR 1.2 (IQR: 0.6-1.4) with SCLs after symblepharon release with OSR (P < 0.001). The median diameter of the SCL used was 15 mm (IQR: 15-16), with a median base curve of 7.9 mm (IQR: 7.9-8). Symblepharon recurrence was noted in 70% of eyes that underwent amniotic membrane grafting; no recurrence was seen with mucous membrane grafting or conjunctival autografting. CONCLUSIONS: In eyes with CCC with keratopathy and symblepharon, visual rehabilitation is possible with SCLs after symblepharon release with OSR without having to resort to a penetrating corneal procedure.

Sequelae of carbide-related thermo-chemical injury: A retrospective analysis.

Purpose: To describe the outcomes of eyes with calcium carbide (CaC2)-related thermo-chemical injury. Methods: This study included 28 eyes of 23 patients who presented with calcium carbide-related ocular burns. Only patients with more than three months of follow-up were included. Group A included 16 eyes with Dua's Grade I-III burns, while Group B included 12 eyes with Grade IV-VI burns. Electronic medical records were reviewed to provide data on the etiology of burn, presenting clinical signs and visual acuity, sequelae, and surgical interventions performed, both in the acute and chronic phases. Results: The overall mean age was 28.48 ± 11.8 years. Fifteen patients were injured while using carbide to create an explosion to scare away animals on farms. The median presenting BCVA (best-corrected visual acuity) in Group A (20/160) was significantly better than in Group B [(20/2000) (P = 0.002)]. Five eyes in Group A and one eye in Group B underwent medical management. There was no difference in the duration of follow-up for both groups (P = 0.24). The median final BCVA in Group A (20/32) was significantly better than in Group B [(20/200) (P = 0.02)]. Two eyes in Group A and nine eyes in Group B developed LSCD. Two eyes in Group B were phthisical at the last visit. Conclusion: Calcium carbide-related ocular injuries can result in significant visual morbidity in young adults. Early presentation and management may improve outcomes. Prevention of these injuries by increasing awareness and increasing advocacy efforts is necessary.

Case Report: Simultaneous penetrating keratoplasty with autologous simple limbal epithelial transplantation as an alternative to keratoprosthesis.

Introduction and importance: This case report highlights the multidisciplinary approach required to achieve successful anatomical and functional outcomes, in an eye with total limbal stem cell deficiency (LSCD) associated with underlying corneal scarring and thinning. Presentation of case: A 59-year-old gentleman had poor visual recovery in the right eye (RE) following accidental carbide blast, 1-year before presenting to us. The visual acuity was counting fingers and clinical examination revealed cicatricial entropion involving the upper eyelid, total LSCD, corneal scarring with a central descemetocele and cataract in the RE. Prior to ocular surface reconstruction, entropion correction was performed. Three months later, penetrating keratoplasty combined with cataract surgery and intraocular lens implantation (penetrating keratoplasty (PK) triple), with autologous simple limbal epithelial transplantation (SLET) was performed. The visual acuity was 20/100, 18 months after the surgery, with a clear well-epithelized corneal graft and stable ocular surface. Discussion: LSCD is caused by a decrease in the population and /or function of the limbal epithelial stem cells. Limbal stem cell transplantation (LSCT) is warranted in eyes with total LSCD. In eyes with coexisting corneal scarring, LSCT alone may be inadequate to restore the vision. These eyes require simultaneous or sequential lamellar or full-thickness corneal transplantation for visual rehabilitation. Though, the existing literature favors a sequential approach, where LSCT is performed first followed by corneal transplantation, under certain circumstances such as a thin underlying cornea like in our case, corneal transplantation may have to be combined with LSCT to achieve optimal outcomes. Conclusion: Combining autologous SLET with PK can be performed for visual rehabilitation in eyes with unilateral total LSCD and underlying corneal thinning. Corneal and limbal graft survival is prolonged if existing adnexal comorbidities are addressed before any surgical intervention is planned and adequate time interval is allowed for the surface inflammation to subside.

Demographic profile and clinical characteristics of patients presenting with acute ocular burns.

Purpose: To study and compare the demographic and clinical profile of acute ocular burns (AOB) in children and adults. Methods: This retrospective case series included 271 children (338 eyes) and 1300 adults (1809 eyes) who presented to two tertiary eye care centers within one month of sustaining AOB. Data regarding demographics, causative agents, severity of injury, visual acuity (VA), and treatment were collected and analyzed. Results: Males were more commonly affected particularly among adults (81% versus 64%, P < 0.00001). Among children, 79% sustained domestic injuries, whereas 59% of adults had work-place injuries (P < 0.0001). Most cases were due to alkali (38%) and acids (22%). Edible lime (chuna, 32%), superglue (14%), and firecrackers (12%) in children, and chuna (7%), insecticides, lye, superglue (6% each), toilet cleaner (4%) and battery acid (3%) in adults, were the main causative agents. The percentage of cases with Dua grade IV-VI was greater in children (16% versus 9%; P = 0.0001). Amniotic membrane grafting and/or tarsorrhaphy were needed in 36% and 14% of affected eyes in children and adults, respectively (P < 0.00001). The median presenting VA was logMAR 0.5 in children and logMAR 0.3 in adults (P = 0.0001), which improved significantly with treatment in both groups (P < 0.0001), but the final VA in eyes with Dua grade IV-VI burns was poorer in children (logMAR 1.3 versus logMAR 0.8, P = 0.04). Conclusion: The findings clearly delineate the at-risk groups, causative agents, clinical severity, and treatment outcomes of AOB. Increased awareness and data-driven targeted preventive strategies are needed to reduce the avoidable ocular morbidity in AOB.

Vortex Keratopathy as a Presenting Feature of Ocular Mucous Membrane Pemphigoid.

PURPOSE: The aim of this study was to describe the presenting feature of vortex keratopathy in 3 patients with biopsy-proven ocular mucous membrane pemphigoid (OMMP). METHODS: The first patient was a 52-year-old woman with chronic redness and foreign body sensation for 3 years who presented with unilateral vortex keratopathy. Seven months later, in the same eye, she developed conjunctival signs suggestive of OMMP. The second patient was a 33-year-old woman with similar chronic symptoms that were exacerbated by pterygium surgery. Clinical examination revealed vortex keratopathy in the right eye with subtle conjunctival signs suggestive of OMMP. The third patient was a 70-year-old woman with complaints of repeated episodes of redness and foreign body sensation for 18 months who presented with vortex keratopathy in the right eye and conjunctival signs suggestive of OMMP in the same eye. To confirm the clinical diagnosis, bilateral conjunctival biopsy was performed in all patients. RESULTS: OMMP was diagnosed based on conjunctival signs and confirmed on direct immunofluorescence positivity, demonstrating antibodies characteristic and diagnostic of OMMP in the basement membrane zone. A unique feature that preceded or coexisted with the conjunctival signs was unilateral vortex keratopathy seen in all 3 patients, independent of the stage of the disease at which they presented. CONCLUSIONS: Vortex keratopathy can be a presenting feature in patients with OMMP. A complete ocular surface examination, especially checking the medial canthus for keratin and the inferior fornix for foreshortening, is necessary. Conjunctival biopsy should be performed in all cases to confirm the clinical diagnosis wherever required.

Keratoprosthesis in dry eye disease.

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.

Contact lenses in dry eye disease and associated ocular surface disorders.

Dry eye disease (DED) is prevalent in all age groups and is known to cause chronic ocular discomfort and pain, and greatly affects the quality of life. Patients with ocular surface disease (OSD) may also have reduced tear secretion due to lacrimal gland damage, thus leading to aqueous deficient DED. Even with conventional management modalities such as lubricating eyedrops, topical corticosteroids, autologous serum eyedrops, or punctal plugs, many patients continue to suffer from debilitating symptoms. Contact lenses are increasingly being used in OSD providing surface hydration, protection from environmental insults, mechanical damage from abnormal lids, and as a modality for constant drug delivery to the ocular surface. This review describes the role of soft lenses and rigid gas-permeable scleral lenses in the management of DED associated with OSD. The efficacy of contact lenses, lens selection, and optimal lens fit are reviewed for specific indications.

Role of topical and systemic immunosuppression in aqueous-deficient dry eye disease.

Immunosuppression in aqueous-deficient dry eye disease (ADDE) is required not only to improve the symptoms and signs but also to prevent further progression of the disease and its sight-threatening sequelae. This immunomodulation can be achieved through topical and/or systemic medications, and the choice of one drug over the other is determined by the underlying systemic disease. These immunosuppressive agents require a minimum of 6-8 weeks to achieve their beneficial effect, and during this time, the patient is usually placed on topical corticosteroids. Antimetabolites such as methotrexate, azathioprine, and mycophenolate mofetil, along with calcineurin inhibitors, are commonly used as first-line medications. The latter have a pivotal role in immunomodulation since T cells contribute significantly to the pathogenesis of ocular surface inflammation in dry eye disease. Alkylating agents are largely limited to controlling acute exacerbations with pulse doses of cyclophosphamide. Biologic agents, such as rituximab, are particularly useful in patients with refractory disease. Each group of drugs has its own side-effect profiles and requires a stringent monitoring schedule that must be followed to prevent systemic morbidity. A customized combination of topical and systemic medications is usually required to achieve adequate control, and this review aims to help the clinician choose the most appropriate modality and monitoring regimen for a given case of ADDE.

Aqueous-deficient dry eye disease: Preferred practice pattern guidelines on clinical approach, diagnosis, and management.

Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one-third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long-term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well-being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology-based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADDE.

Optimization and evaluation of tear protein elution from Schirmer's strips in dry eye disease.

PURPOSE: Extraction of tear protein from Schirmer's strip is a prerequisite for the proper identification and screening of biomarkers in dry eye disease. The study compares different methods of extraction of tear proteins from the Schirmer's strip. METHODS: Reflex tear was collected from healthy controls (HC; n = 12), Stevens-Johnson syndrome (SJS; n = 3) and dry eye disease (DED; n = 3) patients using capillary tube. This tear was used to measure the volume absorbed by Schirmer's strip per microliter. Different buffers (6) were used to compare the protein yield from the Schirmer's strip in four different conditions. The tear proteins extracted using the highest protein yield buffer were analyzed by mass spectrometry. RESULTS: A linear relationship between the tear volume and wetting length was observed (r = 0.0.997, n = 6). The highest yield was observed after incubation of the Schirmer's strip in 100 mM ammonium bicarbonate (ABC) with 0.25% Nonidet P-40(NP-40) at 4°C for an hour (P < 0.00005). The in-solution digestion of tear eluted in the above condition 100 Mm ABC + 0.25% NP-40 with one-hour incubation yielded a total of 2119 proteins in HC, SJS, and DED. The unique protein observed in SJS and DED was 0.6% and 17.9%, respectively. The significantly expressed proteins are associated with innate immune response, proteolysis, wound healing, and defense response. CONCLUSION: A method for extraction of protein from Schirmer's strip was optimized for increase in protein yield from the tear sample. SJS and DED tear samples have unique protein signature. The study will aid in better design of tear protein-based experimental study.