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Purpose: To evaluate the efficacy of preoperative topical brimonidine use to maintain visibility during trabeculectomy and control intraoperative bleeding and postoperative subconjunctival hemorrhage., Methods: The first group comprised 35 eyes of 34 patients administered brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops 6 and 3 min before surgery, and 33 eyes of 31 patients who received no medication for vasoconstriction formed the second group. Preoperative and postoperative photographs and operation video images were taken and vision analysis software used. Black-and-white images were obtained to identify the blood vessel and surface hemorrhage areas. The surface area of the hemorrhage was calculated by counting the black pixels with Image J software., Results: There was no significant difference between two groups in terms of baseline (preoperative) eye redness (p > 0.05). In the first group, the eye redness values were 344.7 ± 19.5 pixels preoperatively and 244.1 ± 23.3 pixels at the beginning of the surgery, respectively (p < 0.001). However, no significant change was observed in the second group in eye redness (348.2 ± 17.5 pixels preoperatively and 360.7 ± 26.8 pixels at the beginning of the surgery, p > 0.05). Cautery was used for an average of 11.91 ± 1.96 s in the first group and 25.57 ± 4.66 s in the second to control intraoperative bleeding (P < 0.001)., Conclusion: Preoperative topical brimonidine use in trabeculectomy surgery significantly decreased intraoperative bleeding and postoperative subconjunctival hemorrhage and facilitated bleeding control.

Purpose: Ocular manifestations of immunoglobulin G4 (IgG4)-related disease are common in children although remain ill-defined because of the disease's rarity. We describe a pediatric case of IgG4-related orbital disease (IgG4-ROD) who presented with persistent conjunctival infiltration before developing lacrimal gland enlargement 3 years later., Methods: This was a case report., Results: An 8-year-old girl developed forniceal salmon-patch-like conjunctival lesions in her left eye that were refractory to topical corticosteroids. Investigations, including an orbital MRI and 2 conjunctival biopsies, were negative for lymphoma. She was treated with topical corticosteroids and then nonsteroidal antiinflammatory drops. The lesions decreased mildly, and no new lesion emerged. After 3 years, the patient developed a ptosis, new salmon-patch conjunctival lesions, and papillae. Vision deteriorated to 20/80 because of severe punctate epithelial erosions in the left eye, and the Schirmer test was significantly reduced. A repeat MRI revealed an enlarged left lacrimal gland. A biopsy was performed and was compatible with IgG4-ROD. An elevated IgG4 level of 4.61 g/L was also found. The patient was successfully treated with oral prednisone but flared on tapering the dosage. Rituximab was therefore initiated with excellent clinical response, and prednisone was discontinued. Vision returned to 20/20 after aggressive lubrification, punctal plugs, and autologous serum eye drops. Tear function came back to normal, and local treatments were stopped., Conclusions: This case describes a pediatric case of IgG4-ROD presenting initially with conjunctival follicular reaction, later developing lacrimal gland involvement. Therefore, it is important to consider IgG4-ROD in chronic atypical follicular conjunctival lesions in children, even in the absence of orbital disease., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Conjunctival cicatrizing conditions are vision threatening, with poor outcomes despite aggressive systemic therapy. This study tests the utility of serial injections of 5-fluorouracil (5-FU) into the fornices to treat conjunctival scarring in patients with ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis., Methods: Retrospective cohort study. Fisher exact test and multivariable logistic regression analyses were used to compare clinical outcomes of patients who were administered 5-FU injections versus patients who were not injected. Model fit was examined for multivariable regression., Results: One hundred twelve eyes (56 patients) met the inclusion criteria. Thirty-eight eyes (34%) had Stevens-Johnson syndrome/toxic epidermal necrolysis, and 74 eyes (66%) were diagnosed with ocular cicatricial pemphigoid. Twenty-five eyes received ≥1 injection of 5-FU. Sixteen eyes received 1-4 injections, while 9 received ≥5. Median follow-up until last encounter was 18 months. Analysis of each disease entity alone and in combination revealed that 5-FU injections were associated with improvement in final visual acuity, corneal scarring, trichiasis, need for/number of mucous membrane graft surgeries, and severity of symblephara., Conclusions: Serial injection of 5-FU in the affected fornices is a promising treatment for severe vision-threatening conjunctival scarring from ocular cicatricial pemphigoid and Stevens-Johnson syndrome/toxic epidermal necrolysis. Given the excellent safety profile of 5-FU around the eye, the solid biologic foundation for using 5-FU in this setting, and the severe risk of vision loss from these disorders, the authors suggest that serial 5-FU injections be adopted as therapy for conjunctival scarring from ocular cicatricial pemphigoid or Stevens-Johnson syndrome/toxic epidermal necrolysis despite the limitations of this retrospective study., Competing Interests: A.K. is a consultant to Genentech, Roche, Horizon Therapeutics, and Stryker Corp., none of which had any relationship to this study. The other authors have no conflicts of interest to disclose., (Copyright © 2020 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: A prospective, open-label study in 20 professional swimmers evaluated the efficacy and safety of an ophthalmic solution containing crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS in releasing eye irritation and restoring ocular surface damages after prolonged exposure to chlorinated water., Methods: Individually, one eye was instilled with the ophthalmic solution and the other used as a comparator. Eye drops were self-administered three times a day for 2 months. Tear film breakup time (primary endpoint), Schirmer I test, beating of eyelashes/min, tear osmolarity, corneal and conjunctival staining with fluorescein, Ocular Surface Disease Index questionnaire, subject satisfaction, visual acuity (secondary endpoints), and Efron Grading Scale were evaluated at screening/baseline (V1), week 1 (V2), week 2 (V3), week 4 (V4), and week 8 (V5)., Results: After 2 months, breakup time test significantly improved in the treated eyes (+1.67 s) compared to control (-3.00 s) ( p  = 0.0002). Corneal and conjunctival surfaces of treated eyes recovered significantly compared to control eyes when assessed by fluorescein staining ( p  < 0.0001), Ocular Surface Disease Index ( p  < 0.05), and visual analog scale ( p  = 0.0348) scores. Improvements were also observed with Schirmer I test, beating of eyelashes, and tear osmolarity, despite without statistical significance. Efron Grading Scale was consistent with the other tests. The ocular tolerability was excellent., Conclusion: The adequate combination of crosslinked hyaluronic acid, coenzyme Q10, and vitamin E TPGS, contained in the ophthalmic solution VisuXL ® , has been shown to protect ocular surface from potential damages originating from prolonged exposure to chlorinated water. VisuXL may represent a compelling treatment in other situations beyond dry eye syndrome.

Purpose : To evaluate the effect of intra-lesional injection of Trichloroacetic acid (TCA) 10% in patients with conjunctival inclusion cysts. Methods : This prospective case series study included all patients with conjunctival inclusion cyst who were referred to our referral center from August 2016 to August 2018. All patients received TCA 10% injection into the conjunctival cyst, and outcomes of the intervention were evaluated at least 6 months later. Results : Ten patients with mean age of 24 ± 17.6 (range 6-65) years including three children received TCA 10% injection into the conjunctival cyst. We included 6 anophthalmic and 4 ophthalmic cases. All patients were treated successfully and no recurrence of the lesion was observed in any case. Mean follow up duration was 18.1 ± 8.3 (range 6-28) months. Conclusion : Intra-lesional injection of TCA 10% is a safe, simple, and effective treatment in patients with conjunctival inclusion cysts including ophthalmic cases and anophthalmic cases, both in adults and in children. This concentration may avoid ocular surface complications.

Conjunctival epithelial inclusion cysts are an infrequent complication in anophthalmic sockets. The ocular prosthesis may become difficult to retain or it may cause local discomfort. Treatment options described include surgical resection, marsupialisation, and the use of injected sclerosing agents. We present a case of a 27-year-old female who developed a conjunctival epithelial inclusion cyst two years after a left eye evisceration. This invariably caused the ocular prosthesis to become cosmetically unacceptable. Trichloroacetic acid 20% (TCA) was injected intracystically as a minor procedure at the slit lamp. Four months later there was no recurrence of the cyst and the prosthesis retained an excellent position in the socket. This case highlights the successful treatment of a conjunctival epithelial inclusion cyst with TCA (20%) without the need for a surgical procedure.

Rationale: Conjunctival papilloma is a benign neoplastic lesion of epithelial origin, with a minimal tendency toward malignancy and an exophytic growth type. Etiological factors that contribute to the appearance of papilloma are UV exposure, HPV infection, smoking, and immunodeficiency. A case report of limbal conjunctival papilloma treatment with topical interferon alpha-2b eye drops applied to the conjunctival sac., Patient Concerns: A 49-year-old female patient treated in the Clinical Department of Ophthalmology for conjunctival lesion located in the temporal quadrant near the limbus of the right eye. Ocular examination of the patient's eye did not show any abnormalities: visual acuity-20/20, intraocular pressure-16 mmHg., Diagnoses: During physical examination, a broad-based pink lesion of size 4 mm × 6 mm was found in interpalpebral bulbar conjunctiva with prominent feeder vessels and soft consistency. Lesion in the biomicroscopic examination did not show any sign of malignancy. In Swept Source Optical Coherence Tomography (SS-OCT) there was no sign of infiltration into sclera or cornea. In vivo confocal microscopy (IVCM) examination, revealed loss of the normal conjunctival epithelium - hyper-reflective cells, variation of cell size. A clinical diagnosis of limbal conjunctival papilloma was made., Interventions: Interferon alpha-2b 1 million IU/ml eye drops were applied 4 times a day for 5 months. The treatment lasted 5 months without changing the dosing regimen. Three months after the start of the interferon treatment, a complete regression of the lesion was achieved. Treatment was continued for the following 2 months. Controlled IVCM after 6 months showed only few hyper-reflective cells and fibrotic tissue., Outcomes: Treatment of conjunctival papilloma with topical interferon alpha-2b led to the complete regression of the lesion. Although after the therapy the conjunctiva appears normal both in slit lamp and in the OCT examination, there is a noticeable fibrosis of the tissue in confocal microscopy. During the 14-month follow-up period, there were no recurrent lesions., Lessons: In this study, topical interferon alpha-2b has been shown to be an effective and safe therapy for small-to-medium-size conjunctival papilloma without any sign of malignancy.

Introduction: We report a case of patient who underwent bilateral eyeball tattoo procedure for cosmetic purpose complicated with intraocular dye injection which led to ocular inflammation, secondary glaucoma, and cataract., Case Description: A 21-year-old female presented to emergency department with severe right eye pain and photophobia 21 days after conjunctival tattooing procedure. Slit-lamp examination revealed right-sided eyelid edema and black deposits of tattoo ink under the bulbar conjunctiva. Dye deposits were also present in anterior chamber, covering corneal endothelium, iris and anterior lens' capsule. Ocular inflammation and secondary glaucoma were diagnosed. The patient underwent surgical treatment to control ocular inflammation. Intraocular pressure remained stable after Nd:YAG iridotomy and on topical drugs. Moreover, during the follow-up, in contralateral eye, we observed "conjunctival lumps"-local hypersensitivity reaction to the dye, which were asymptomatic to the patient., Conclusion: Eyeball tattooing complications are new challenges that ophthalmologist may have to face nowadays. We also reviewed for the first time possible complications of eyeball tattooing described in available literature.

Objective: To evaluate tissue levels, safety, and efficacy of topical ophthalmic 0.5% and 1% pirfenidone in decreasing subconjunctival fibrosis., Animal Studied: Twelve normal beagle dogs PROCEDURES: A 5 × 1 mm diameter silicone disk was implanted subconjunctivally in one eye, and then dogs were treated with topical 0.5% pirfenidone (n = 9) in artificial tears or artificial tears alone (n = 3) for 28 days. To evaluate tissue drug levels, a single sample of tears, conjunctiva, and aqueous humor was collected 30 (n = 3), 90 (n = 3), and 180 min (n = 3) following administration of the last drop of pirfenidone, respectively. Fibrous capsule thickness and staining for Ki67 and fibroblast activation protein alpha (FAPα) were evaluated histologically. After a 2-week washout, the experiment was repeated in the opposite eye and using 1% pirfenidone., Results: Treatment with pirfenidone resulted in thinner fibrous capsules and decreased staining for FAPα with no adverse effects. The implant in one dog treated with pirfenidone extruded. There was no difference in tissue levels, capsular thickness, or staining for Ki67 or FAPα between dogs treated with 0.5% or 1% pirfenidone., Conclusions: Pirfenidone may decrease fibrosis following glaucoma shunt surgery and can potentially be used indefinitely due to minimal side effects., (© 2019 American College of Veterinary Ophthalmologists.)

Competing Interests: Competing interests: None declared.

Objectives: To evaluate the in vitro effects of 1-mM rebamipide ophthalmic solution on the expression of inflammatory cytokines and MUC5AC in Cu, Zn-superoxide dismutase-1 (SOD-1) knock-down conjunctival epithelium., Methods: Conjunctival epithelium from C57BL/6 wild-type mice was cultured and treated with rebamipide ophthalmic solution. Using cytometric bead array, we examined the levels of interleukin-(IL)-6, IL-10, IL-17, monocyte chemoattractant protein-1, interferon-γ (INF-γ), tumor necrosis factor, and IL-12p70 in the culture supernatants. The culture supernatants were obtained from the culture medium of nontreated or SOD-1 knock-down conjunctival epithelium using small interfering RNA (siRNA). In addition, ELISA was performed to ascertain the MUC5AC concentration in the culture medium., Results: After rebamipide ophthalmic solution was applied, IL-6 concentration in the supernatants of conjunctival epithelial cells treated with and without siRNA showed a significant timewise decrease from 0 to 24 hr (963±42 to 0.07±0.05 pg/mL and 932±168 to 2.2±0.05 pg/mL, respectively) (P<0.001). Compared with baseline values, MUC5AC concentrations significantly increased 24 hr after rebamipide application to the conjunctival cultures-both with and without SOD-1 siRNA treatment (P<0.05 in both cases)., Conclusions: Rebamipide seems to increase MUC5AC levels and suppress inflammation by decreasing IL-6 levels in mouse conjunctival epithelial cell cultures. SOD-1 siRNA-treated mouse conjunctival epithelial cell culture is a practical method for investigating changes in mucosa-associated mucins and proinflammatory cytokines in response to therapeutic interventions.

Purpose: To report a case of Laryngeal Onycho Cutaneous Syndrome in a 10 year old child presenting with an ocular surface mass., Methods: A 10 year old boy presented in the out-patient department with a painless mass in left eye. There was history of airway obstruction requiring tracheotomy in early childhood and recurrent skin ulcerations. Aslit lamp examination revealed fleshy mass arising from the supero-nasalconjunctiva of left eye. Systemic examination revealed ulcerative lesions on cheeks and ears with dystrophic nails in hands and feet., Results: The ocular surface lesion was treated successfully with topical steroid drops., Conclusion: Steroids may be useful in treating early lesion of ocular surface in LOCS. The importance of regular follow must be emphasized for timely management of frequent granulation tissue outgrowth in bid to avoid development of severe symblepharon and blindness., (© NEPjOPH.)

Background: Sustained drug delivery is a large unmet clinical need in glaucoma. Here, we incorporated a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor, CCG-222740, into slow release large unilamellar vesicles derived from the liposomes DOTMA (1,2-di-O-octadecenyl-3-trimethylammonium propane) and DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine), and tested their effects in vitro and in vivo., Results: The vesicles were spherical particles of around 130 nm and were strongly cationic. A large amount of inhibitor could be incorporated into the vesicles. We showed that the nanocarrier CCG-222740 formulation gradually released the inhibitor over 14 days using high performance liquid chromatography. Nanocarrier CCG-222740 significantly decreased ACTA2 gene expression and was not cytotoxic in human conjunctival fibroblasts. In vivo, nanocarrier CCG-222740 doubled the bleb survival from 11.0 ± 0.6 days to 22.0 ± 1.3 days (p = 0.001), decreased conjunctival scarring and did not have any local or systemic adverse effects in a rabbit model of glaucoma filtration surgery., Conclusions: Our study demonstrates proof-of-concept that a nanocarrier-based formulation efficiently achieves a sustained release of a Myocardin-Related Transcription Factor/Serum Response Factor inhibitor and prevents conjunctival fibrosis in an established rabbit model of glaucoma filtration surgery.

Purpose of Review: This review offers recommendations for monitoring disease status in ocular cicatricial pemphigoid as well therapeutic options including local and systemic therapies., Recent Findings: A negative biopsy on direct immunofluorescence does not preclude a diagnosis of OCP. If a patient's cicatrization is active and/or progressive, systemic immunosuppression should be commenced., Summary: OCP is a chronic systemic autoimmune disease that requires systemic immunosuppression.

Purpose: Topical timolol has been increasingly demonstrated to be an effective treatment for pyogenic granulomas (PG). The authors review the treatment outcomes of 17 patients with ocular PG treated with topical timolol., Methods: Retrospective interventional study of 17 patients with ocular PGs treated with timolol 0.5% solution. Patient demographics, clinical features, treatment response, and recurrence were noted., Results: Nine females and 8 males with a mean age of 23 years (range, 3-67 years) were included. Mean duration of disease prior to treatment was 3.81 months (range, 0.25-11 months). Etiologies included chalazia (12 cases, 71%), postsurgical (4, 24%) and trauma (1, 6%). Five patients (29%) had treatment with topical steroids prior to presentation. Fifteen patients (88%) had PG located on the palpebral conjunctiva and 2 (12%) involving the bulbar conjunctiva. Mean lesion size was 5.06 × 6.06 mm (range, 3-8 × 3-18 mm). Fifteen patients (88%) had complete lesion resolution with a mean treatment duration of 3.07 weeks (range, 2-5 weeks) and no adverse events or recurrences with a mean follow up of 9.47 months (range, 6-27 months). Two patients (12%) underwent lesion excision after 6 weeks of timolol failed to yield resolution., Conclusion: Topical timolol appears to be a well-tolerated nonsurgical treatment of ocular PG in both children and adults. Clinicians may wish to consider topical timolol to treat PG as opposed to topical steroids, given the inherent risk of steroid response ocular hypertension and the difficulty to measure intraocular pressure in younger children who require general anesthesia for excision.

Purpose: To report a case of ocular findings associated with chronic eosinophilic pneumonia (CEP)., Case: A 63-year-old man was referred to the National Institution of Hospital Organization Tokyo Medical Center with bilateral eyelid swelling due to giant papillomatous changes, each measuring approximately 10 mm in diameter with severe hyperemia on the tarsal conjunctiva. He was followed for CEP for 8 years and systemically treated with 6 mg oral prednisolone for an average of 5 years. Because the lesions did not respond to topical 0.1% tacrolimus and 0.025% levocabastine treatment and because an increase in intraocular pressure was found to occur as a side effect of 0.01% betamethasone instillation for several months, we performed surgical resection of the bilateral conjunctival lesions. Histopathological findings revealed extreme eosinophil, plasma cell, and lymphocytic infiltration and interstitial fibrosis. These conjunctival specimen findings were similar to those seen in the alveolar lesions in CEP. Topical antiinflammatory therapy using 0.1% tacrolimus eye drops was administered after surgery, which relieved the patient's lid swelling and itching. However, the lesions concurrently changed to be consistent with exacerbation and remission of systemic CEP., Conclusions: Based on the clinical course and histopathology, the conjunctival proliferative masses in our case were assumed to be associated with CEP.

We report two cases of Loa loa (eye worm) infection in Iceland; the former in a 35-year-old woman born in Africa but living in Iceland for several years; the latter in a 31-year- old woman who had traveled in Africa. Both women sought medical attention due to discomfort in one eye. On exami-nation a worm was noted in both cases, moving under the conjunctiva, 3 cm in length and 0.5 mm in diameter. Both patients also had symptoms from the extremities; episodic swelling and itching in the former case, and muscle pain in the latter. Both patients were diagnosed with loiasis with Calabar swellings of the extremities and were successfully treated with albendazole and diethylcarbamazine. Increased awareness is needed for infections which previously have been rare in the Nordics.

Purpose: To assess the extraocular muscle thickness and chemosis after treatment with tocilizumab in patients with active Graves' ophthalmopathy by optical coherence tomography., Methods: Case series of five patients with active Graves' ophthalmopathy (clinical activity score ≥4/10) treated with 4 doses of tocilizumab. These patients had been previously treated with corticosteroids with no response. Spectral-domain optical coherence tomography was employed to determine lateral and medial rectus muscle thickness and chemosis before and after 4 doses of tocilizumab given monthly. Scanning was performed at 3 and 9 o'clock (nasal and temporal)., Results: The study included four women and one man with a median age of 52 years (range: 38-73). Median Graves' ophthalmopathy activity duration was 17 months (12-18). Median medial rectus and determine lateral thicknesses pre-treatment were 249μm (174-366) and 337μm (142-443), respectively. Median chemosis was 409μm (290-610). After tocilizumab treatment, median muscle thicknesses reduced to 157μm (88-187) and 197μm (99-290), respectively (P=.043; Wilcoxon) and chemosis to 59μm (0-78). Median clinical activity score decreased from 5 (4-8) to 1 (0-3)., Conclusions: A reduction in extraocular muscle thickness and chemosis was observed after treatment with tocilizumab in Graves' ophthalmopathy patients using an optical coherence tomography, so this technique could be a useful complementary technique to assess the therapeutic responses., (Copyright © 2018 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To evaluate the presence of atopy in patients with ocular cicatricial pemphigoid (OCP)., Method: Patient encounters between August 2005 and November 2016 at the Massachusetts Eye Research and Surgery Institute (MERSI) were searched to identify those with biopsy-proven OCP who had concurrent evidence of atopy., Results: There were 230 patients with biopsy-proven OCP. Thirty-three of them were found to have clinical symptoms of atopy (asthma, hay fever, and eczema) and of these, 23 had evidence of atopy in their conjunctival biopsy specimens. All patients were administered immunomodulatory therapy for treatment of their OCP with 20 patients requiring additional antiallergy treatment to control residual atopic ocular symptoms. Among patients who used antiallergy medications, 80% showed improvement in residual symptoms. Rituximab and/or intravenous immunoglobulin is a preferred OCP medication for patients with OCP with some evidence of atopy., Conclusions: Clinicians should consider the coexistence of atopy in patients with OCP, especially in those with persistent symptoms after initiation of immunomodulatory therapy.

Purpose: To evaluate whether long-term remission of ocular cicatricial pemphigoid (OCP) after withdrawal of immunomodulatory therapy (IMT) is possible., Methods: A total of 34 of 464 presenting patients (66 eyes) with biopsy-proven OCP in long-term remission off IMT were identified after finishing a 2-year IMT regimen without active disease (2005-2015). Long-term remission off IMT for OCP was defined as patients withdrawn from IMT ≥1 year lacking clinically detectable progressive scarring according to Foster staging and subjective assessment., Results: All 34 patients achieved ≥1 year of clinical remission without IMT following 2 years IMT lacking active disease. Mean onset age of OCP was 67.0 years, and median follow-up time was 63.4 months. Mean duration between OCP onset and IMT initiation was 29.5 months, with a mean sustained remission time of 36.0 months off IMT. The mean duration of IMT prior to remission off IMT was 34.8 months (median 32 months, IQR 27-39.5 months). Commonly, methotrexate was used prior to OCP remission (19 patients; 55.9%). Two patients experienced mild flare-up postremission off IMT at months 25 and 37 and a course of topical steroid appeared to resolve the inflammation. Another patient had active inflammation at last office visit 5 years after discontinuation of IMT and will restart IMT., Conclusions: Long-term remission for OCP off IMT may be achieved after stepladder IMT is implemented and withdrawn. Longer follow-up and more sensitive measures of scarring and inflammation are needed to generate a consensus on the definition of complete remission and on cessation of systemic IMT for OCP.

Purpose: We determine the effects of bevacizumab on collagen production in a mouse model of conjunctival scarring., Methods: Experimental surgery was performed as described for the mouse model of conjunctival scarring, and bevacizumab was introduced by conjunctival injection. The capacity of bevacizumab to recognize conjunctival VEGF-A was determined by ELISA. Col1a1 was measured by real-time PCR and immunoblotting. T cells and collagen were visualized by immunofluorescence and picrosirius red staining of bleb cryosections. Conjunctival CD4+ or CD8a+ T cells were counted by flow cytometry. Mouse splenic T cells were cultured with bevacizumab/IgG and their numbers, cell cycle, and collagen production were measured using a cell counter, flow cytometry, and sircol soluble collagen assay, respectively. Reconstitution experiments in severe combined immunodeficiency (SCID) mice were performed by injection of freshly isolated T cells on day 2 postoperatively., Results: Bevacizumab recognized approximately 20% of endogenous murine VEGF-A. Injection of bevacizumab raised Col1a1 expression in the blebs at mRNA and protein levels. Bevacizumab did not induce collagen in conjunctival fibroblasts, but increased CD4+ and CD8a+ cell numbers as well as collagen production by these cells. Collagen appeared to accumulate in the vicinity of T cells in the bevacizumab-treated blebs. While SCID blebs did not show elevated collagen levels, reconstitution with CD4+ or CD8a+ cells resulted in increased Col1a1 expression at mRNA and protein levels., Conclusions: Bevacizumab increased collagen production in the mouse model of conjunctival scarring. This collagen induction was mediated by T cells that were also stimulated by bevacizumab to increase in numbers.

Significance: The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures. Clinicians are often faced with red eyes with no apparent underlying pathology. Low-dose brimonidine reduced ocular redness in such subjects with efficacy maintained over 1 month and negligible rebound redness., Purpose: The aim of this study was to evaluate the safety and efficacy of brimonidine tartrate ophthalmic solution 0.025% for the treatment of ocular redness., Methods: In this single-center, double-masked, phase 3 clinical trial, adult subjects with baseline redness of more than 1 unit in both eyes (0- to 4-unit scale) were randomized 2:1 to brimonidine 0.025% or vehicle. A single dose was administered in-office (day 1); thereafter subjects instilled treatment four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days post-treatment). Efficacy end points included investigator-evaluated redness 5 to 240 minutes post-instillation on day 1 (primary); investigator-evaluated change from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5 minutes post-instillation on days 15 and 29; total clearance of redness, and subject-assessed redness. Safety/tolerability measures included adverse events, rebound redness, and drop comfort., Results: Sixty subjects were randomized (n = 40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with brimonidine versus vehicle over the 5- to 240-minute post-instillation period (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point within that period (P < .0001). At 1, 360, and 480 minutes post-instillation, respectively, the mean differences (95% confidence interval) between treatments were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10), respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29, and minimal rebound redness was observed following discontinuation. Adverse events were infrequent, and brimonidine was rated as very comfortable., Conclusions: Brimonidine 0.025% appeared safe and effective for reduction of ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis, and negligible rebound redness.

Purpose: To describe a case of reactive lymphoid hyperplasia (RLH) of the conjunctiva responding to cyclosporine immunosuppressant monotherapy., Methods: A 66-year-old man with a 2-year history of biopsy-proven bilateral RLH presented for dry eye evaluation with chief complaints of burning, stinging, and irritation in both eyes. After slit-lamp examination and positive findings of matrix metalloproteinase 9 in the patient's tear film, he was diagnosed with meibomian gland dysfunction and tear-insufficiency dry eye disease. The patient was subsequently treated with topical cyclosporine (ophthalmic emulsion 0.5 mg/mL two times per day) in both eyes., Results: Examination at the 3-month follow-up visit revealed significant reduction of the RLH lesions bilaterally., Conclusions: This report represents the first case of benign ocular RLH responsive to topical cyclosporine therapy. We believe that cyclosporine could play a role in treating patients with benign ocular RLH and warrants further investigation to evaluate its full efficacy.

Purpose: It was hypothesized that tear protein biomarkers could predict the effects of topical steroid treatment and desiccating stress in patients with dry eye disease (DED). To test this concept, a randomized, double-masked, controlled clinical trial with 41 patients was conducted., Methods: The patients were treated topically with either 0.1% fluorometholone (FML) or polyvinyl alcohol (PA). Tear samples were collected using 1 μl glass capillaries at recruitment into the study and after a 3-week treatment period, both before and after 2 h exposure to desiccating stress, in a controlled environment chamber. Relative quantification of tear proteins was conducted by NanoLC-MSTOF using sequential window acquisition of all theoretical mass spectra (SWATH). Ocular surface integrity (corneal and conjunctival staining and conjunctival hyperemia) was selected as the key DED-related sign and analyzed with proteomic data. Analysis of covariance (ANCOVA) and linear models were used to analyze the data with R., Results: 758 proteins were identified and relatively quantified from each tear sample. Analysis revealed 9 differentially expressed proteins between FML and PA treatments after 3 weeks and 7 after desiccating stress (P < 0.05). We also identified several differentially expressed proteins at the initial collection, which could be used to predict changes of conjunctival and corneal staining and conjunctival hyperemia after FML treatment and after desiccating stress. These proteins include complement C3 (C3) and calmodulin like 5 (CALML5), which could also differentiate the severity of DED at baseline., Conclusions: The identified proteins could be further used as biomarkers to identify patients most benefiting from FML treatment., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Chronic use of topical hypotensive therapies in glaucoma patients leads to chronic inflammation of the ocular surface, which decreases the success rate of long-term glaucoma management. The aim of this study is to evaluate the effect of topical palmitoylethanolamide (PEA) (Defluxa © ), a well-known anti-inflammatory and analgesic agent, in suppressing the ocular surface inflammation associated with the use of hypotensive eye drops., Methods: In a pilot clinical trial, we enrolled 15 glaucomatous patients who received topical PEA (Defluxa) in addition to the current antiglaucoma drugs, while 15 glaucomatous patients did not receive any additional treatment. At 3 different time points (day 0, 15, and 30), signs of ocular surface involvement, adverse events, visual acuity, and intraocular pressure were assessed., Results: Topical PEA (Defluxa) was effective in increasing the Schirmer test (P < 0.05) and the tear film breakup time (T-BUT) (P < 0.0001), and improving the conjunctival hyperemia (P < 0.0001) by day 30, compared to baseline. Compared to control, by day 15, the conjunctival hyperemia score was significantly decreased in the PEA (Defluxa) group (P < 0.01), while the T-BUT and the Schirmer Test achieved a significant improvement by day 30 (P < 0.05; P < 0.01)., Discussion: Our data suggests that topical PEA (Defluxa) is a safe, effective, and generally well-tolerated treatment to prevent or suppress ocular surface inflammation attributable to chronic glaucoma treatment.

Introduced in 2008 and subsequently popularized in South Korea, cosmetic eye whitening has been offered as a treatment of chronic conjunctival hyperemia. Patients undergo conjunctivectomy with topical mitomycin C (MMC) 0.02% application to achieve a whitened appearance from bleaching of avascular sclera. Much speculation has arisen from this procedure given the limited available evidence on its efficacy and safety. A literature search was performed to review common complications of cosmetic eye whitening, including chronic conjunctival epithelial defects, scleral thinning, avascular zones in the sclera, dry eye syndrome, and diplopia requiring strabismus surgery. Informing the general public of the risks of this procedure is of great importance for dermatologists and other cosmetic surgeons.

Purpose: Fibrotic scarring after ocular surgeries and chemical burn injuries can impede clarity of the cornea and cause vision impairment. Transforming growth factor β (TGFβ) signaling pathway is known to mediate fibrotic scarring, and NADPH oxidase-derived reactive oxygen species has been shown to be an effector molecule that facilitates TGFβ1-mediated responses. The present study explores the expression profile and functional importance of NADPH oxidase (Nox) in conjunctival fibroblasts. In addition, the effect of curcumin on the TGFβ1-induced NADPH oxidase expression and collagen synthesis was also investigated., Methods: The mRNA expression of Nox isoforms in rabbit conjunctival fibroblasts was measured by real-time PCR. The production of hydrogen peroxide (H2O2) and total collagen by these cells was measured by Amplex Red assay and Picro-Sirius red assay, respectively. Nox4 was knocked down by adenovirus-mediated siRNA targeting Nox4 (Adv-Nox4i)., Results: We describe for the first time that conjunctival fibroblasts express mRNA encoding for Nox2, Nox3, Nox4, and Nox5. TGFβ1 was found to induce Nox4 mRNA expression and total collagen release by these cells (P < 0.05; n = 4), and both responses are blocked by Smad3 inhibitor SIS3. Suppressing Nox4 gene transcription with Adv-Nox4i completely attenuated TGFβ1-stimulated H2O2 release and collagen production by conjunctival fibroblasts (P < 0.05; n = 4-6). Similarly, curcumin also inhibited TGFβ1-induced Smad3 phosphorylation, Nox4-derived H2O2 production, and total collagen synthesis by conjunctival fibroblasts (P < 0.05; n = 4-6)., Conclusions: The present study suggests that TGFβ1-mediated production of collagen by conjunctival fibroblasts involves Nox4-derived H2O2 pathway and this effect of Nox4 is abrogated by curcumin. This mechanism might be exploited to prevent fibrotic scarring after surgeries and chemical burn injuries in the eye.

Blau syndrome is an early-onset granulomatous disease known to affect the skin, joints, and eyes. We report a child with diffuse rash, arthritis, and subconjunctival nodules. Biopsy of the bulbar conjunctiva revealed noncaseating lipogranulomas that lead to a diagnosis of Blau syndrome. To our knowledge, noncaseating lipogranulomas of the conjunctiva have not been reported previously as a presenting finding in Blau syndrome. Although uveitis is the classic manifestation, it is important to broaden the awareness of other ocular signs, as these variations can aid in diagnosis., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Ocular/periocular involvement in pemphigus vulgaris (OPV) has rarely been reported. The objective of the present study was to investigate the pattern of OPV and define the prognostic value of its manifestation., Patients and Methods: From 1985 to 2014, a total of 167 patients with pemphigus vulgaris (PV) were treated at four tertiary Spanish hospitals. In this retrospective study, we included all patients with OPV. Clinical data and information on associated symptoms were obtained from patients' medical records., Results: Only 24 (14.3 %) of all PV patients had ocular lesions. In most cases, -ocular involvement was preceded by PV lesions at various other sites (mean duration: 33.7 months). Ocular PV lesions occurred during flares of mucocutaneous pemphigus, and was never the only mucosal manifestation. The most common clinical signs were conjunctival hyperemia (87.5 %), erosions on the eyelids (41.6 %) as well as of the palpebral/bulbar conjunctiva (33.3 %) and at the medial epicanthus (20.8 %). The most relevant associated symptoms included local pain/stinging (71.4 %), irritation (47.6 %), photophobia (38.1 %), and epiphora (23.9 %). Ocular PV improved with systemic and adjuvant topical therapies. Only two patients experienced sequelae., Conclusions: In patients with PV, ocular involvement is an exception. Ocular PV is associated with greater disease activity, and usually follows a benign course. Sites affected are the conjunctiva, the eyelids, or both., (© 2017 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

Purpose: To describe an unusual cicatrizing manifestation of periocular amyloid and the utility of adjuvant antimetabolite therapy., Methods: This is a case report of a 49-year old woman with progressive bilateral upper lid ptosis, who was found to have bilateral inferior forniceal masses with thickening of the conjunctiva. Conjunctival and eyelid biopsies showed evidence of amyloid deposition. Systemic evaluation did not reveal any evidence of systemic amyloidosis. Her blepharoptosis continued to deteriorate, and she underwent bilateral sequential upper lid ptosis correction surgery and debulking procedures. Subsequently, she developed severe and progressive cicatricial conjunctivitis with extensive symblepharon formation in all 4 fornices and restriction of ocular motility, simulating a clinical picture of ocular mucous membrane pemphigoid., Results: She was treated surgically by division of symblepharon augmented with application of topical mitomycin C intraoperatively. This has been partially successful in freeing up differential movement between her lid and her eye and consequently improving eye protection and lubrication., Conclusions: Pseudopemphigoid represents a rare manifestation of periocular amyloid. Risks and benefits of surgical procedures in this context need to be carefully weighed to minimize the risk of secondary complications. Topical mitomycin C may be considered as a relatively safe adjunct in managing the cicatricial component of the disease.

Importance: Pyogenic granulomas, acquired vascular lesions, form on the ocular or palpebral surface related to inflammation from chalazia, trauma, or surgery. They can be unsightly, spontaneously bleed, and cause irritation to patients., Observations: A case series is presented of 4 consecutive children with acquired ocular surface pyogenic granulomas treated at Boston Children's Hospital from 2014 to 2016 with only topical timolol, 0.5%, twice daily for a minimum of 21 days. In all cases, complete resolution occurred within the treatment period with no recurrence for at least 3 months. There were no adverse effects from the timolol during follow-up., Conclusions and Relevance: This case series of 4 children, while limited to no greater than 12 weeks of follow-up and without control children, suggests that ocular surface pyogenic granulomas respond to topical timolol treatment, which has a lower adverse-effect profile than conventional topical steroid treatments or other medical or surgical therapies. If confirmed in larger studies with longer follow-up and controls, this may be the desired treatment modality.

Conjunctival actinic keratosis is rare and difficult to treat, as recurrences are common. Imiquimod, an immune response modulator, is currently Food and Drug Administration-approved for cutaneous actinic keratosis and superficial basal cell carcinomas. Emerging reports have shown it to be effective in treating some periocular and conjunctival lesions. The authors present a case of a 68-year-old white man with recurrent actinic keratosis involving the pretarsal conjunctiva, which was successfully treated with 5% topical imiquimod following previous failure with cryotherapy and interferon α-2b. The patient had ocular irritation that resolved on cessation of treatment. To the authors' knowledge, this is the first report of conjunctival actinic keratosis being treated with and successfully eradicated by topical imiquimod.

Purpose: To investigate the current status of corneal and conjunctival disorders due to antitumor drugs in Japan. Methods: Questionnaires on corneal and conjunctival disorders due to antitumor drugs were sent to members of the Japan Cornea Society, and data on patients' background, clinical findings, treatment and prognosis of cases between January 2009 and December 2011 were collected and analyzed. Results: Out of all 221 cases from 66 facilities, TS-1Ⓡ had been administered in 210 cases (95.0%). Corneal findings were noted in 192 cases (86.9%), including 161cases (72.9%) of superficial punctate keratopathy, 55 cases (24.9%) of epithelial crack line, 38 cases (17.2%) of sheet-like epithelial abnormality, and 15 cases (6.8%) of corneal erosion. Conjunctival and ciliary findings were observed in 49 cases (22.2%). Lacrimal obstruction and constriction were found in 81cases (36.7%). Logistic regression analyses revealed the discontinuation and switching of antitumor drugs as the significant factor of good prognosis of clinical signs and visual acuity in cases with TS-1Ⓡ administration. Conclusions: Although corneal and conjunctival disorders due to antitumor drugs, especially TS-1Ⓡ, are important adverse effects, the only effective treatment at this time is the discontinuation and switching of antitumor drugs. Future prospective studies are needed to elucidate pathogenesis, aiming to the prediction and prevention of the occurrence.

PurposePhaeohyphomycosis are melanin-containing fungi that rarely infect the eye. We describe three cases of ocular infection with some unusual clinical features.MethodsSeries of three case reports describing three different presentations of phaeohyphomycosis of the eye, their histopathology, and management.ResultsCase 1 mimicked an inflamed conjunctival naevus and was excised on this basis, revealing a conjunctival retention cyst containing pigmented fungal hyphae. Case 2 showed a wooden foreign body incidentally associated with pigmented fungal hyphae, which required treatment with topical antifungal therapy. Case 3 clinically was thought to be a perforated uveal melanoma and comprised an extensive plaque of pigmented fungal hyphae over ulcerated cornea.ConclusionThe pigmented melanin containing hyphae of phaeohyphomycosis mimicked melanocytic lesions in two cases and was an incidental finding in the context of a surface foreign body.

Purpose: To report a novel intervention for the treatment of conjunctival lymphangiectasia-subconjunctival injection of bevacizumab., Methods: A 53-year-old white male presented with a 3-month history of right ocular discomfort and redness unresponsive to conventional topical treatment of lubricants and steroids. A clinical diagnosis of conjunctival lymphangiectasia was confirmed by biopsy. Bevacizumab (25 mg/mL) was injected subconjunctivally into the affected area., Results: An improvement in the degree of conjunctival chemosis was evident at 5 days postinjection. At 1-month follow-up, symptoms had fully resolved. No recurrence had been observed at 3 years' follow-up., Conclusions: Subconjunctival bevacizumab injection may be an effective treatment for conjunctival lymphangiectasia.

Purpose: To examine the clinical characteristics and medium-term outcomes of unsutured scleral flap trabeculectomies., Patient and Methods: A retrospective review of 45 patients who underwent 50 unsutured scleral flap trabeculectomies by a single ophthalmic surgeon. Information pertaining to each patient's demographic details, preoperative assessment, surgical procedure, and 2 years of postoperative management were obtained., Results: The average age of patients was 72.4±12.5 (range, 30 to 97) years. The diagnosis was primary open-angle glaucoma in 38 (76.0%) cases. The average preoperative, 1 year postoperative and 2-year postoperative intraocular pressure (with number of topical antiglaucoma medications) were 20.8 (2.5), 13.2 (0.4), and 12.6 mm Hg (0.7), respectively. The procedure performed was a trabeculectomy alone in 32 (64.0%) cases, and combined trabeculectomy and phacoemulsification in 18 (36.0%) cases. Four were performed with mitomycin C. Three procedures (6%) had intraoperative complications (2 iris prolapses, 1 subconjunctival hemorrhage). Seven procedures were complicated by a postoperative choroidal detachment, which were managed conservatively and resolved spontaneously over time. There was 1 case (2%) of postoperative hypotony, which failed to resolve (intraocular pressure of <6 mm Hg for >3 months)., Conclusions: The majority of unsutured scleral flap trabeculectomies had an acceptable risk profile and resulted in a decrease in the intraocular pressure at 2 years postoperatively.

Purpose: To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD)., Design: Phase 1/2 prospective, randomized, double-masked clinical trial., Participants: Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled., Methods: Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen., Main Outcome Measures: Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI)., Results: After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P = 0.04)., Conclusions: Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)