Anny M. S. Cheng

Recent advances on ocular Demodex infestation.

Purpose of review To summarize recent advances on ocular Demodex infestation. Recent findings Demodex infestation is a potential cause of ocular surface inflammation. The pathogenesis of Demodex in eliciting ocular surface inflammation has been further clarified. Cliradex is currently the treatment of choice, it comprises the most active ingredient of tea tree oil, that is terpinen-4-ol, which helps eradicate Demodex mites and reduce ocular surface inflammation. Summary Ocular demodicosis is a common but overlooked eye disease that manifests a number of morbidities. Demodex folliculorum causes chronic anterior blepharitis whereas Demodex brevis causes posterior blepharitis, meibomian gland dysfunction, recurrent chalazia, and refractory keratoconjunctivitis. The lash sampling and microscopic counting method and in-vivo confocal microscopy are key diagnostic methods. Cliradex shows promising potential to reduce Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.

Morselized Amniotic Membrane Tissue for Refractory Corneal Epithelial Defects in Cicatricial Ocular Surface Diseases.

Purpose To evaluate the clinical efficacy of morselized amniotic membrane and umbilical cord tissue (MAU) in treating refractory corneal epithelial defect in ocular cicatricial diseases. Methods Retrospective review of four patients with ocular cicatricial diseases treated with topical MAU for corneal epithelial defects refractory to conventional treatments including topical lubricants, autologous serum, bandage contact lens, and tarsorraphy. Their symptoms, corneal staining, conjunctival inflammation, and visual acuity were compared before and after treatment. Results After topical application of MAU twice daily, two patients demonstrated rapid corneal epithelialization with prompt visual acuity improvement at the first day. All patients showed corneal epithelialization in 7.3 ± 2.6 days accompanied by a significant relief of symptoms, reduction of ocular surface inflammation, and improvement of visual acuity. Conclusion This pilot study suggests topical MAU can be developed into a novel treatment for treating refractory corneal epithelial defects. Translational Relevance Topical MAU can be an effective novel treatment for refractory corneal epithelial defects.

Restoration of Fornix Tear Reservoir in Conjunctivochalasis With Fornix Reconstruction.

Purpose: To determine whether conjunctivochalasis (CCh) obliterates the fornix tear reservoir and to discern whether there is concomitant aqueous tear deficiency (ATD) dry eye. Methods: Retrospective review of 18 eyes of 12 patients with CCh and ATD (CCh + ATD) and 18 eyes of 13 patients with CCh without ATD (CCh − ATD). Changes were compared before and after fornix reconstruction regarding symptoms, basal tear volumes, use of medications, conjunctival inflammation, and corneal staining. Results: Fornix reconstruction with conjunctival recession and amniotic membrane transplantation effectively restored the fornix tear reservoir as evidenced by a significant increase of the basal tear volume in both CCh − ATD and CCh + ATD groups. Multivariate regression analysis confirmed that such improvement was significantly correlated with symptomatic resolution (r = 1, P < 0.001), which was also accompanied by significant resolution of corneal staining, conjunctival inflammation, and reduction of topical medications. Intriguingly, the prior diagnosis of ATD was no longer existent in 10 of the 18 eyes (56%) with CCh + ATD suggesting that ATD could be secondary to obliteration of the fornix tear reservoir by CCh. Conclusions: Obliteration of the fornix tear reservoir is a common pathogenic process regardless of whether CCh is associated with ATD dry eye. Restoration of the tear reservoir by fornix reconstruction with conjunctival recession and amniotic membrane transplantation results in significant resolution of symptoms and signs associated with ATD that is secondary to CCh and helps identify genuine ATD dry eye that is independent of CCh.

Corneal Nerve Regeneration after Self-Retained Cryopreserved Amniotic Membrane in Dry Eye Disease

Purpose To evaluate the efficacy of self-retained cryopreserved amniotic membrane (CAM) in promoting corneal nerve regeneration and improving corneal sensitivity in dry eye disease (DED). Methods In this prospective randomized clinical trial, subjects with DED were randomized to receive CAM (study group) or conventional maximum treatment (control). Changes in signs and symptoms, corneal sensitivity, topography, and in vivo confocal microscopy (IVCM) were evaluated at baseline, 1 month, and 3 months. Results Twenty subjects (age 66.9 ± 8.9) were enrolled and 17 completed all follow-up visits. Signs and symptoms were significantly improved in the study group yet remained constant in the control. IVCM showed a significant increase in corneal nerve density in the study group (12,241 ± 5083 μm/mm2 at baseline, 16,364 ± 3734 μm/mm2 at 1 month, and 18,827 ± 5453 μm/mm2 at 3 months, p = 0.015) but was unchanged in the control. This improvement was accompanied with a significant increase in corneal sensitivity (3.25 ± 0.6 cm at baseline, 5.2 ± 0.5 cm at 1 month, and 5.6 ± 0.4 cm at 3 months, p < 0.001) and corneal topography only in the study group. Conclusions Self-retained CAM is a promising therapy for corneal nerve regeneration and accelerated recovery of the ocular surface health in patients with DED. The study is registered at clinicaltrials.gov with trial identifier: NCT02764814.

Topical Cryopreserved Amniotic Membrane and Umbilical Cord Eye Drops Promote Re-Epithelialization in a Murine Corneal Abrasion Model.

Purpose To evaluate morselized amniotic membrane and umbilical cord (AMUC) eye drops in promoting corneal re-epithelialization. Methods Following a 2-mm diameter central epithelial wound in one eye of 48 normal C57BL/6 mouse corneas, 10 μL of saline with (n = 24) or without (n = 24) AMUC was applied three times a day for 6 days. The corneal epithelial defect was measured using 0.1% fluorescein, while corneal epithelial regularity was measured by assessment of a reflected light off the corneal surface. Hematoxylin and eosin and immunohistochemistry was performed for Ki-67, CD45, βIII-tubulin, and keratin12. Safety and toxicity were also assessed by monitoring physical activity and body weight. Results Compared with the vehicle saline control, AMUC resulted in a significantly smaller corneal epithelial defect at 12 hours (P = 0.002), 1 day (P = 0.016), and 2 days (P = 0.04) post abrasion. Amniotic membrane and umbilical cord also achieved a more rapid complete epithelialization (3.15 ± 1.44 vs. 4.00 ± 1.63 days, P = 0.06) and induced a higher incidence of corneal regularity without affecting physical activity and body weight. Spearman correlation showed that epithelialization was significantly correlated with treatment groups (P < 0.001), time (P < 0.001), and corneal regularity (P = 0.04). Amniotic membrane and umbilical cord significantly decreased CD45+ cell infiltration in the peripheral cornea (P < 0.05) and promoted Ki-67+ cells in the central corneal epithelium (P < 0.05). Conclusion Topical AMUC significantly promotes corneal epithelialization and restores corneal regularity by reducing inflammation and promoting proliferation in a murine model of corneal abrasion without causing safety or toxicity concerns. This encouraging preclinical finding warrants a controlled human trial in the future.

Retrospective study to identify trigeminal–cervical ocular referred pain as a new causative entity of ocular pain

Purpose To determine the prevalence and clinical characteristics of trigeminal–cervical (TC) ocular referred pain. Methods A retrospective study of 1,680 patients seen during 2002–2010 was performed in an ocular surface specialty center to identify patients with or without TC pain defined as ocular pain with ipsilateral trigger points located at the occipital region. Patients with refractory TC pain despite topical anesthetics and conventional treatments received interventional injection to each trigger point. Results A total of 81 (4.8%) patients (study group) with TC pain and 241 patients (control group) without TC pain were identified out of the 1,680 patients over an 8 year period. There was no difference in age, gender, prior surgeries, medications, non-pain symptoms, pain laterality, and concomitant ocular diseases between the 2 groups. Multivariate regression analysis showed that patients with TC pain had a significant correlation with persistent deep ocular pain, ipsilateral trigger points (f2=99, p<0.001) but not headaches (f2=0.09, p=0.5). Injection at the trigger points achieved complete or partial pain resolution with a low recurrence rate in 43 of 45 (96%) patients with TC pain. Conclusion TC pain defined herein may be a different entity of ocular pain and can indeed be differentiated from other ocular pain by the referral character so that one may avoid mislabeling it as undetermined or as a reason to unnecessarily overtreat concomitant ocular diseases.

Celecoxib and Pioglitazone as Potential Therapeutics for Regulating TGF-β-Induced Hyaluronan in Dysthyroid Myopathy.

PURPOSE To investigate the role of extraocular muscles (EOM) myoblasts in Graves ophthalmopathy (GO) pathology and the effect of a cyclooxygenase (COX)-2 inhibitor and a peroxisome proliferator-activated receptor (PPAR)-γ agonist in its treatment. METHODS Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-γ, insulin-like growth factor (IGF)-1, IL-1β, and TNF-α, and the effect on PPAR-γ, COX-2, TGF-β, and thyroid stimulating hormone receptor (TSH-R) expressions were assessed using real-time (RT)-PCR, ELISA, and Western blot. The effect of a COX-2 inhibitor and a PPAR-γ agonist on the expression of TGF-β, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated. RESULTS Real-time PCR showed significant upregulation in PPAR-γ, COX-2, TGF-β, and TSH-R mRNA expression in GO myoblasts when treated with TNF-α but not in the non-GO. While IFN-γ and IGF-1 had no significant effect, IL-1β did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor α-induced TGF-β in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-γ agonist substantially diminished this TNF-α-induced TGF-β, HA, and HAS3 expression. CONCLUSIONS These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-γ agonist in this study are potential treatments for GO due to their ability to suppress TNF-α-induced TGF-β, HAS, and HA upregulation.

Effect of Trypan Blue on Descemet Membrane Elasticity

Purpose: To evaluate the effect of trypan blue on the elastic property of Descemet membrane (DM) by atomic force microscopy. Methods: Human corneas (n = 10) were obtained from the Illinois Eye Bank (Chicago, IL). The DM was isolated and divided into two halves, one half was stained with ophthalmic trypan blue (Vision Blue, 0.06%, DORC International), whereas the unstained other half served as control. The DM samples were then tested using the atomic force microscope. Data were analyzed using the Hertz model for the evaluation of the Young modulus of elasticity. Results: Atomic force microscopy showed higher cantilever deflection on trypan blue–stained DM compared with control, and the difference was statistically significant (P = 0.03). Force–distance curve analysis also revealed a statistically significant increase in the Young modulus of elasticity in the trypan blue–stained samples (10.5 ± 1.4 kPa) compared with the control (5.8 ± 0.8 kPa), (P < 0.0001). Conclusions: Our results suggest that trypan blue may decrease DM elasticity and consequently increase its stiffness. This may influence the graft adherence when used for endothelial keratoplasty.

Recent Advances in Conjunctivochalasis

Conjunctivo chalasis (CCh) presents as loose and redundant conjunctival folds interspersed between the globe and eyelids and may cause a variety of ocular symptoms that mimic dry eye. It disturbs the preocular tear film by blocking the tear drainage, disrupting the tear meniscus, and obliterating the fornix tear reservoir to interfere tear flow from the fornix reservoir to the tear meniscus. Elimination of intrinsic irritative stimuli/inflammation by topical preservative-free dexamethasone is the initial treatment for delayed tear clearance (DTC) associated CCh. After differentiating dry eye caused by CCh from that caused by aqueous tear deficiency (ATD) and determining that CCh is the cause of ocular symptoms, restoration of the fornix tear reservoir by fornix reconstruction with conjunctival recession and amniotic membrane transplantation is an effective surgical procedure to treat CCh. After elimination of CCh, punctal occlusion remains ultimate and specific management of genuine ATD dry eye. Identification of DTC, symptomatic CCh and evaluation of genuine ATD dry eye that is independent of CCh led physicians to adopt an effective treatment algorithm to restore the integrity of the ocular surface.

Safety and efficacy of 4-terpineol against microorganisms associated with blepharitis and common ocular diseases

Objective Microbial infection has been reported to cause blepharitis, conjunctivitis and keratitis. We evaluated the safety and efficacy of a foam formulation of 2% 4-terpineol (T4O) against common ocular microorganisms. Material and methods The antimicrobial effect of a 2% T4O formulation was evaluated by the United States Pharmacopeia 51 (USP <51>) antimicrobial effectiveness test for 14 and 28 days, as well as by a Time Kill Study (ASTM E2315) with a 60 s exposure time. Its potential of causing skin and ocular irritation was evaluated by the Repeated Insult Patch Test and the Hen’s Egg Chorioallantoic Membrane Test, respectively. Results and discussion It was seen that 2% T4O formulation did not cause ocular irritation, skin irritation, sensitisation or allergic contact dermatitis in human subjects. Most importantly, it killed microorganisms listed in USP <51> at both 14 and 28 days and exerted a rapid killing effect within 60 s against 13 bacteria, 1 fungus and Acanthamoeba castellanii. Conclusion The above finding suggests that 2% T4O formulation is safe and effective in killing microorganisms related to common ocular and skin infective diseases. Translational relevance Although the clinical efficacy in treating ocular disease was not directly studied; this foam formulation containing 2% T4O, based on the in vitro results of this work, demonstrated that it can potentially be used as a preservative-free cleansing agent for ocular hygiene maintenance due to its ability to exert a broad-spectrum antimicrobial effect without causing ocular or skin irritation.