OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy.

BACKGROUND: To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment. METHODS: Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed. RESULTS: A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001-1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890-220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915-0.990, P = 0.014). CONCLUSION: Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.

Familial autosomal recessive bestrophinopathy: identification of a novel variant in BEST1 gene and the specific metabolomic profile.

BACKGROUND: Autosomal recessive bestrophinopathy (ARB) is a retinal degenerative disorder caused by BEST1 mutations with autosomal recessive inheritance. We aim to map a comprehensive genomic and metabolomic profile of a consanguineous Chinese family with ARB. METHODS: Ophthalmic examinations were performed on the affected patients with ARB. The proband was screened for potential causative mutations in a panel with 256 known retinal disease genes by using target capture sequencing. The related mutation was further validated and segregated in the family members by Sanger sequencing. In silico prediction tools were used for pathogenicity assessment. A UHPLC-MS/MS metabolomic analysis was performed to explore the disease-associated metabolic feature. RESULTS: The affected patients from this family were characterized by low vision, the presence of subretinal fluid, macular edema, and hyperopia with coincidental angle closure. DNA sequencing identified a novel missense mutation in the BEST1 gene c.646G > A (p.Val216Ile) of the proband. Sanger sequencing further confirmed the mutation. The missense mutation was co-segregation across the pedigree and predicted to be deleterious by SIFT (0.017). The blood metabolic profiles were highly similar among all family members probably because of the same lifestyle, habitat and genomic background. However, ARB patients presented a significant deregulation of metabolites, such as citric acid, L-Threonic acid, and eicosapentaenoic acid. CONCLUSIONS: We identified a novel disease-associated variant in the BEST1 gene as well as a disease-specific metabolic feature in familial ARB. Our findings helped improve the understanding of ARB mechanisms.

Minimal surgery achieved good visual acuity in selected patients with magnetic intravitreal foreign body and traumatic cataract.

BACKGROUND: To explore minimal surgery in selected patients with intravitreal foreign body (IVFD) and traumatic cataract. METHODS: Twelve eyes of 12 patients with small ferrous IVFD and traumatic cataract without endophthalmitis, retinal injury and secondary glaucoma, between September 2015 and March 2017 were retrospectively analyzed. Primary removal of IVFD was performed by external magnetic extraction through the pars plana incision. Secondary removal of traumatic cataract by phacoemulsification and intraocular lens (IOL) implantation with or without anterior vitrectomy were performed. Patients were followed up at 1 day, 1 week, 1 month, 3 months, 6 months and 12 months after surgery. RESULTS: All patients were male with a mean age of 32 years old. All IVFDs were successfully removed without retinal injury. Two to 6 months later, the traumatic cataract was successfully removed by phacoemulsification combined with IOL implantation in the capsule bag in 10 patients. Anterior vitrectomy was implied in 2 patients with large posterior capsule rupture, and the IOLs were placed in the ciliary sulcus. Best-corrected visual acuity ranged from hand movement to 20/100 before surgery and improved ranging from 20/32 to 20/20 at the final follow-up. The IOLs were well centered. Complications such as secondary glaucoma, endophthalmitis and retinal detachment were not found. CONCLUSIONS: Primary removal of small ferrous IVFD by external magnetic extraction followed by secondary cataract removal and IOL implantation is an appropriate choice. Minimal surgery may obtain good visual outcome without complications in selected patients.

Pterygium surgery combined with the removal of a missed occult iris foreign body detected incidentally during pterygium examination: a case report.

BACKGROUND: An occult foreign body may be retained in patient with small self-sealing wound and no decreased visual acuity without complete examination. Here we report a case of a retained occult ferrous iris foreign body detected incidentally during pterygium examination. CASE PRESENTATION: A 69-year-old man presented to our ophthalmology department because of foreign body sensation and persistent redness in both eyes for 2 years. In the left eye, a pterygium, paracentral corneal opacity and a vertically oval pupil were observed. Ultrasound biomicroscopy and gonioscopy revealed a retained metallic-like foreign body partially embedded in the inferior peripheral iris. Pterygium surgery and the removal of the retained iris foreign body were performed simultaneously. No recurrent pterygium or residual foreign body was found during follow-up. CONCLUSIONS: A thorough history should be obtained and complete physical examination should be performed in patients with ocular self-sealing wounds to prevent missed intraocular foreign bodies, which may result in potential sight-threatening ocular complications.

SURGICAL REMOVAL OF DENSE POSTERIOR CAPSULE OPACIFICATION AND VITREOUS FLOATERS IN ADULTS BY POSTERIOR CONTINUOUS CURVILINEAR CAPSULORHEXIS THROUGH THE PARS PLANA AND 23-GAUGE VITRECTOMY.

PURPOSE: To evaluate the safety and efficacy of posterior continuous curvilinear capsulorhexis through the pars plana and 23-gauge vitrectomy in surgical management of dense posterior capsule opacification and vitreous floaters. METHODS: Fifteen pseudophakic eyes of 15 patients with dense posterior capsule opacification and vitreous floaters between September 2012 and June 2014 were included; after vitrectomy, posterior continuous curvilinear capsulorhexis through the pars plana was performed. Data were collected, including baseline preoperative characteristics, postoperative outcomes, complications, and a modified quality-of-life survey that patients completed. RESULTS: No intraoperative or postoperative complications were encountered in any of the 15 cases. Mean Snellen best-corrected visual acuity was 20/250 preoperatively and improved to 20/32 postoperatively (P < 0.001). All patients showed normal intraocular pressure 7 days after the procedure. The mean overall corneal endothelial cell loss at postoperative Month 3 was 1.2%. Approximately 80% of the patients had no complaint of vitreous floaters after the procedure. Except for 1 patient (7%) diagnosed with age-related macular degeneration, the rest of the patients (93%) were satisfied with the procedure and would recommend it to friends with dense posterior capsule opacification and vitreous floaters. CONCLUSION: Posterior continuous curvilinear capsulorhexis through the pars plana combined with 23-gauge vitrectomy may be used to remove dense posterior capsule opacification and vitreous floaters in pseudophakic eyes.

Osmoprotectants suppress the production and activity of matrix metalloproteinases induced by hyperosmolarity in primary human corneal epithelial cells.

PURPOSE: Hyperosmolarity has been recognized as a proinflammatory stress in the pathogenesis of dry eye disease. This study investigated the suppressive effect of osmoprotectants (L-carnitine, erythritol, and betaine) on the production and activity of matrix metalloproteinases (MMPs) in primary human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. METHODS: Primary HCECs were established from fresh donor limbal tissue explants. The cultures in iso-osmolar medium (312 mOsM) were switched to hyperosmotic media with or without prior incubation with different concentrations of L-carnitine, erythritol, or betaine (2, 10, or 20 mM). The mRNA expression of the MMPs was determined with reverse transcription and quantitative real-time PCR (RT-qPCR). Protein production and activity were evaluated with immunofluorescent staining and gelatin zymography. RESULTS: Hyperosmotic media (400, 450, or 500 mOsM) significantly stimulated mRNA expression of collagenase MMP-13, gelatinases MMP-9 and MMP-2, stromelysin MMP-3, and matrilysin MMP-7, mostly in an osmolarity-dependent fashion. The stimulated mRNA expression and protein production of these MMPs were significantly but differentially suppressed by L-carnitine, erythritol, or betaine, as evaluated with RT-qPCR and immunofluorescent staining. Interestingly, these osmoprotectants not only suppressed production but also inhibited activation of MMP-9 and MMP-2, as evaluated with gelatin zymography. CONCLUSIONS: Our findings for the first time demonstrate that osmoprotectants, L-carnitine, erythritol, and betaine, suppress the gene expression, protein production, and enzymatic activity of MMPs in HCECs exposed to hyperosmotic stress. L-carnitine appears to have the broadest and strongest suppressive effect on these MMPs. These osmoprotectants may have potential effects in protecting ocular surface epithelia from MMP-mediated disorders in dry eye disease.

Topical interferon-gamma neutralization prevents conjunctival goblet cell loss in experimental murine dry eye.

Evidence suggests that the cytokine interferon (IFN)-γ released by natural killer and CD4(+) T cells contributes to the conjunctival goblet cell (GC) loss in dry eye. The purpose of this study was to investigate if topical neutralization of IFN-γ prevents or alleviates GC loss in an experimental desiccating stress (DS) model of dry eye. In this study, we found that topical IFN-γ neutralization significantly decreased DS-induced conjunctival GC loss. This was accompanied by decreased epithelial apoptosis, and increased IL-13 and decreased FoxA2 expression in the forniceal conjunctiva. To establish that IFN-γ produced by pathogenic CD4(+) T cells contributes to DS-induced GC loss, adoptive transfer of CD4(+) T cells isolated from DS exposed donors to naïve RAG-1(-/-) recipient mice was performed. Similar to the donor mice, topical IFN-γ neutralization decreased conjunctival GC loss, suppressed apoptosis and increased IL-13 expression in adoptive transfer recipients. In summary, this study demonstrated that topical neutralization of IFN-γ prevents GC loss via modulating apoptosis and maintaining IL-13 signaling.

A potential link between bacterial pathogens and allergic conjunctivitis by dendritic cells.

The association and mechanism of bacteria linking to the allergic inflammation have not been well elucidated. This study was to explore a potential link between bacterial pathogens and allergic conjunctivitis by dendritic cells (DCs). Bone marrow-derived DCs from BALB/c and MyD88 knockout mice were treated with or without bacterial pathogens or thymic stromal lymphopoietin (TSLP). Two murine models of the topical challenge with LPS or flagellin and experimental allergic conjunctivitis (EAC) were used for in vivo study. The mRNA expression was determined by reverse transcription and real time PCR, and protein production was evaluated by ELISA, Western blotting, immunofluorescent staining and flow cytometry. TSLP mRNA and protein were found to be largely induced by DCs challenged with microbial pathogens, highly by lipopolysaccharide (LPS) and flagellin. The expression of MyD88, NFκB1, NFκB2 and RelA accompanied by NFκB p65 nuclear translocation and TSLP induction were significantly stimulated by flagellin, but blocked by TLR5 antibody or NFκB inhibitor in DCs from MyD88(+/+) but not MyD88(-/-) mice. TSLP promoted the expression of CD40, CD80, OX40 ligand (OX40L), IL-13 and CCL17 by DCs. TSLP-producing DCs were identified in vivo in ocular surface conjunctiva and draining cervical lymph nodes from two murine models of topical challenge with LPS or flagellin, and EAC in BALB/c mice. TSLP/TSLPR/OX40L signaling was observed in DCs of EAC mice. Our findings demonstrate that DCs not only respond to TSLP, but also produce TSLP via TLR/MyD88/NFκB pathways in response to bacterial pathogens, suggesting a potential link between bacteria and allergic disease.

Transcription factor TCF4 maintains the properties of human corneal epithelial stem cells.

TCF4, a key transcription factor of Wnt signaling system, has been recently found to be essential for maintaining stem cells. However, its signaling pathway is not well elucidated. This study was to explore the functional roles and signaling pathway of TCF4 in maintaining adult stem cell properties using human corneal epithelial stem cells as a model. With immunofluorescent staining and real-time polymerase chain reaction, we observed that TCF4 was exclusively expressed in the basal layer of human limbal epithelium where corneal epithelial stem cells reside. TCF4 was found to be well colocalized with ABCG2 and p63, two recognized epithelial stem/progenitor cell markers. Using in vitro culture models of primary human corneal epithelial cells, we revealed that TCF4 mRNA and protein were upregulated by cells in exponential growth stage, and RNA interference by small interfering RNA-TCF4 (10-50 nM) transfection blocked TCF4 signaling and suppressed cell proliferation as measured by WST-1 assay. TCF4 silence was found to be accompanied by downregulated proliferation-associated factors p63 and survivin, as well as upregulated cyclin-dependent kinase inhibitor 1C (p57). By creating a wound healing model in vitro, we identified upregulation and activation of ß-catenin/TCF4 with their protein translocation from cytoplasm to nuclei, as evaluated by reverse transcription-quantitative real-time polymerase chain reaction, immunostaining, and Western blotting. Upregulated p63/survivin and downregulated p57 were further identified to be TCF4 downstream molecules that promote cell migration and proliferation in wound healing process. These findings demonstrate that transcription factor TCF4 plays an important role in determining or maintaining the phenotype and functional properties of human corneal epithelial stem cells.

A Modified Technique for Preventing Lens-Iris Diaphragm Retropulsion Syndrome in Vitrectomized Eyes during Phacoemulsification.

BACKGROUND: Lens-iris diaphragm retropulsion syndrome (LIDRS) is common in vitrectomized or high myopic eyes during phacoemulsification. We evaluated the results of a modified technique for cataract treatment using phacoemulsification in vitrectomized eyes. METHODS: In this retrospective study, we enrolled thirty-four vitrectomized eyes treated with modified phacoemulsification (Modified Group) and nineteen vitrectomized eyes treated with routine phacoemulsification (Control Group). The modified technique comprised irrigation with a balanced salt solution underneath the pupil before phacoemulsification instrument entry, lens implantation and stromal hydration to stabilize the anterior chamber and equilibrate the pressure between the anterior chamber and posterior cavity. RESULTS: We compared the incidences of intra and postoperative complications and visual outcomes between modified and routine phacoemulsification. Pain, LIDRS and difficulty in stromal hydration were significantly more common in the Control Group than in the Modified Group (p < 0.05). There were no significant differences in the rates of posterior capsular rupture, iris trauma, lens dislocation, or posterior capsular opacification between the Modified and Control Groups (p > 0.05). However, there was no significant difference in visual acuity between the groups (p > 0.05). Complications such as loss of nuclear fragments into the vitreous cavity, cystoid macular edema, retina redetachment, suprachoroidal hemorrhage and vitreous hemorrhage did not occur either intra or postoperatively in any of our patients. CONCLUSIONS: Our modified technique prevents LIDRS and complications arising during cataract surgery in vitrectomized eyes. Aside from this, the results of modified and routine phacoemulsification are similar in vitrectomized eyes.

Short ragweed pollen triggers allergic inflammation through Toll-like receptor 4-dependent thymic stromal lymphopoietin/OX40 ligand/OX40 signaling pathways.

BACKGROUND: Allergic diseases affect a large population. Pollen, an ubiquitous allergen, is the trigger of seasonal rhinitis, conjunctivitis, and asthma, as well as an exacerbating factor of atopic dermatitis. However, the underlying mechanism by which pollen induces thymic stromal lymphopoietin (TSLP)-triggered allergic inflammation through epithelial innate immunity is largely unknown. OBJECTIVE: We sought to explore whether short ragweed (SRW) pollen induces TSLP/OX40 ligand (OX40L)/OX40 signaling through Toll-like receptor (TLR) 4-dependent pathways in patients with allergic disease. METHODS: Three models were used for this study, a well-characterized murine model of allergic conjunctivitis induced by SRW pollen, a topical challenge model on the murine ocular surface, and a culture model of primary human corneal epithelium exposed to aqueous extract of defatted SRW pollen (SRWe). RESULTS: The topical challenges with SRW pollen generated typical allergic conjunctivitis in BALB/c mice. Clinical signs, stimulated TSLP/OX40L/OX40 signaling, and T(H)2 cytokine levels in the ocular mucosa and draining cervical lymph nodes were significantly reduced or eliminated in TLR4-deficient (Tlr4-d) or myeloid differentiation primary response gene 88 (MyD88) knockout (MyD88(-/-)) mice compared with those seen in their wild-type littermates. SRWe stimulated TSLP production by ocular epithelia in wild-type but not Tlr4-d or MyD88(-/-) mice. SRWe-stimulated TSLP was blocked by TLR4 antibody and nuclear factor κB inhibitor in murine and human corneal epithelia. CONCLUSION: For the first time, we have shown that SRW pollen, acting as a functional TLR4 agonist, initiates TLR4-dependent TSLP/OX40L/OX40 signaling, which triggers T(H)2-dominant allergic inflammation. These findings shed light on the understanding of mucosal epithelial innate immunity and create new therapeutic targets to cure allergic diseases.

Single-string, closed-loop fixation modification to reposit a dislocated triple-looped haptic intraocular lens.

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.

Visual Loss Caused by Central Retinal Artery Occlusion After Bee Sting: A Case Report.

A bee sting can lead to an extremely rare case of visual loss caused by central retinal artery occlusion (CRAO). In this study, we report a 66-year-old healthy woman who was referred to our Eye Center because of visual loss, which had occurred after bee sting 2 days earlier. The visual acuity was no light perception (NLP). Examination revealed left eyelid edema, conjunctiva congestion, a 6-mm fixed pupil, scattered retinal hemorrhage, and white-appearing ischemic retina with one small area of the normal-appearing retina temporal to the optic disk. Fundus fluorescein angiography revealed CRAO with one cilioretinal artery sparing. Her systemic workup revealed hypersensitivity, hypercoagulable state, myocardial damage, and hepatic damage. After topical and systemic treatments, the visual acuity was still NLP with improved systemic workup. In brief, CRAO may occur after bee sting, and visual acuity should be monitored for early diagnosis.

Clinical Characteristics and Visual Outcomes in Patients with Intralenticular Foreign Bodies with Self-Sealing Corneal Penetrating Wounds.

PURPOSE: Siderosis bulbi may occur as a result of retained intralenticular foreign bodies (ILFBs) that were missed during examination in patients with self-sealing wounds and without a significant decrease in visual acuity. This study aimed to explore the clinical characteristics and visual outcomes of ILFBs with self-sealing corneal penetrating wounds. METHODS: Fifteen eyes of 15 patients with ILFBs and self-sealing corneal penetrating wounds, seen between October 2014 and September 2019, were retrospectively analyzed. Data regarding the patient demographics, clinical features, surgical procedure, and initial and final best-corrected visual acuity (BCVA) were analyzed. RESULTS: All patients were male with a mean age of 41 years. The foreign bodies passed through the cornea, sometimes through the iris, through the anterior capsule, and finally localized in the lens. All ILFBs were pointed and metallic objects and were successfully removed with phacoemulsification and posterior chamber intraocular lens (IOL) implantation. Anterior capsule violation was found in three eyes, but no posterior capsule rupture was found. The IOL was placed in a capsule bag in all the cases. The BCVA ranged from 20/200 to 20/25 preoperatively and improved to between 20/32 and 20/20 at the last follow-up visit. The IOLs were well-centered. Apart from posterior capsule opacity in four eyes, no other postoperative complications were found. CONCLUSIONS: In patients with a pointed metallic ILFB and self-sealing corneal penetrating wounds (with or without cataracts), early diagnosis and removal of the metallic ILFB combined with lens removal and IOL implantation may avoid late complications and achieve good visual outcomes.

Optical Coherence Tomography Angiography-Based Quantitative Assessment of Morphologic Changes in Active Myopic Choroidal Neovascularization During Anti-vascular Endothelial Growth Factor Therapy.

Purpose: To establish quantitative profile of the morphologic changes among patients with active myopic choroidal neovascularization (mCNV) before and after anti-vascular endothelial growth factor (VEGF) therapy using optical coherence tomography angiography (OCTA) to assess the therapeutic response. Methods: Patients with active mCNV who received anti-VEGF injections between February 2017 to October 2020 and fit the study criteria were retrospectively reviewed. Quantitative analysis of their OCTA images were carried out to evaluate the morphologic features and vascular changes of mCNV lesions in response to anti-VEGF therapy. For further quantitative profiling, mCNV area, fractal dimension, vessel area, vessel density, vessel diameter, vessel length, vessel junction, junction density, and vessel tortuosity were obtained by means of advanced skeletonization postprocessing analyses. Results: Thirty-one eyes of 29 consecutive patients with OCTA-positive mCNV lesions (mean spherical equivalent: -12.55 ± 3.24 diopters) were included. The 31 cases were divided into two phenotypes at baseline: organized interlacing pattern (83.87%) and disorganized vascular loops pattern (16.13%). The values of mCNV area, fractal dimension, vessel area, vessel length, vessel junction, and junction density decreased remarkably 1 month after the initial anti-VEGF injection (p < 0.001). Although, vessel density, vessel diameter, and vessel tortuosity increased meanwhile, only vessel diameter displayed statistical significance (p = 0.027). Of note, relative ratio analysis showed that vessel junction was the most sensitive biomarker in response to anti-VEGF therapy, reflecting a mean decrease of 50.36%. Sensitivity lowered successively in biomarkers of vessel length, vessel area, junction density, mCNV area, and fractal dimension. In addition, percent change of mCNV area (r = 0.552, p = 0.002), fractal dimension (r = 0.446, p = 0.017), vessel area (r = 0.518, p = 0.005), and vessel length (r = 0.440, p = 0.019) were moderately associated with that of central retinal thickness. Conclusions: The study showed morphological as well as quantitative changes on OCTA responding to anti-VEGF treatment in mCNV patients, among which vessel junctions might be the most predictive biomarker. OCTA-based analysis, providing intuitive images and a large spectrum of quantitative data at the same time, could promote new insights into the therapeutic response assessment in mCNV patients.

Characterization and Management of Late Postoperative Capsular Block Syndrome Following Phacoemulsification or Phacovitrectomy.

PURPOSE: To compare the clinical characteristics of eyes affected by late postoperative capsular block syndrome (CBS) after routine phacoemulsification or phacovitrectomy, and to demonstrate the outcomes of neodymium-doped yttrium-aluminum-garnet (Nd:YAG) capsulotomy and posterior continuous curvilinear capsulorrhexis (PCCC) in the treatment of CBS. DESIGN: Retrospective interventional case series study. METHODS: Twenty-eight patients with late postoperative CBS, comprising 13 eyes after phacoemulsification (Group A) and 15 eyes after phacovitrectomy (Group B), were analyzed. Seventeen patients with minimal (degree I), mild (II), and moderate (III) posterior capsular opacification (PCO) underwent Nd:YAG capsulotomy (Group A, 10 eyes and Group B, 7 eyes), while 11 patients with severe (degree IV) PCO underwent PCCC (Group A, 3 eyes and Group B, 8 eyes). RESULTS: A statistically significant postoperative improvement in best-corrected visual acuity (Group A, P = .0002 and Group B, P = .0070) and a significant postoperative decrease in aqueous flare value (Group A, P = .0077 and Group B, P = .0127) were observed. No significant differences were observed in intraocular pressure, aqueous depth, and diopters (P > .05). No surgical complications were experienced by either group. CONCLUSIONS: Late postoperative CBS had similar characteristics whether it developed after phacoemulsification or after phacovitrectomy. Nd:YAG capsulotomy and the PCCC technique are efficient approaches to mild and moderate PCO and severe PCO with CBS, respectively. PCCC may be a viable alternative for treating dense PCO with CBS in pseudophakic eyes.

Effects of azithromycin on gene expression profiles of proinflammatory and anti-inflammatory mediators in the eyelid margin and conjunctiva of patients with meibomian gland disease.

IMPORTANCE: Topical application of azithromycin suppresses expression of proinflammatory mediators while restoring transforming growth factor ß1 (TGF-ß1) levels as evaluated by eyelid margin and conjunctival impression cytology. OBJECTIVE: To explore the effects of azithromycin therapy on expression of proinflammatory and anti-inflammatory mediators in meibomian gland disease (MGD). DESIGN, SETTING, AND PARTICIPANTS: Case-control study performed in a clinic setting from August 17, 2010, to December 31, 2010. Sixteen patients with posterior blepharitis and conjunctival inflammation due to MGD were treated with azithromycin, 1%, drops for 4 weeks. Impression cytology of the lower eyelid margin and tarsal conjunctiva to measure cytokine expression by quantitative real-time polymerase chain reaction as well as tear collection to measure matrix metalloproteinase 9 (MMP-9) activity were performed once in 8 asymptomatic healthy control participants and 5 times in the 16 symptomatic patients (every 2 weeks for 8 weeks), before, during, and after azithromycin treatment. EXPOSURE: Azithromycin, 1%, drops for 4 weeks. MAIN OUTCOMES AND MEASURES: Cytokine expression in the eyelid margin and conjunctiva, and MMP-9 activity in tears. RESULTS: Compared with a 1-time measurement of 8 healthy participants, among 16 symptomatic patients, the mean (SD; 95% CI) fold change of expression of proinflammatory mediators interleukin 1ß (IL-1ß), IL-8, and MMP-9 increased to 13.26 (4.33; 11.14-15.38; P < .001), 9.38 (3.37; 7.73-11.03; P < .001), and 13.49 (4.92; 11.08-15.90; P < .001), respectively, in conjunctival cells and to 11.75 (3.96; 9.81-13.69; P < .001), 9.31 (3.28; 7.70-10.92; P < .001), and 11.52 (3.50; 9.81-13.24; P < .001), respectively, in the eyelid margin of patients with MGD. In contrast, the mean (SD; 96% CI) fold change of expression of TGF-ß1 messenger RNA (mRNA) decreased to 0.58 (0.25; 0.46-0.70; P = .02) and 0.63 (0.14; 0.56-0.70; P = .02) in conjunctival and eyelid margin cells, respectively, of patients with MGD. Azithromycin, 1%, caused a change in the expression pattern of these mediators toward normal levels during 4 weeks of treatment. Levels of IL-1ß, IL-8, and MMP-9 mRNA remained suppressed, although they rebounded toward pretreatment values 4 weeks after azithromycin withdrawal. Expression of TGF-ß1 increased during treatment and remained at levels similar to the healthy controls after drug withdrawal. Change in tear MMP-9 activity was similar to the pattern of MMP-9 transcripts. CONCLUSIONS AND RELEVANCE: While the study did not control for potential confounding factors over time independent of the intervention that may have contributed to the results, topical azithromycin suppressed expression of proinflammatory mediators and increased expression of TGF-ß1 to normal levels. Increased TGF-ß1 expression may contribute to the anti-inflammatory activity of azithromycin in MGD.