Gene expression signatures in conjunctival fornix aspirates of patients with dry eye disease associated with Meibomian gland dysfunction. A proof-of-concept study.

BACKGROUND: Meibomian gland dysfunction (MGD) is one of the most common conditions in ophthalmic practice and the most frequent cause of evaporative dry eye disease (DED). However, the immune mechanisms leading to this pathology are not fully understood and the diagnostic tests available are limited. Here, we used the nCounter technology to analyze immune gene expression in DED-MGD that can be used for developing diagnostic signatures for DED. METHODS: Conjunctival cell samples were obtained by aspiration from patients with DED-MGD (n = 27) and asymptomatic controls (n = 22). RNA was purified, converted to cDNA, preamplified and analyzed using the Gene Expression Human Immune V2 panel (NanoString), which includes 579 target and 15 housekeeping genes. A machine learning (ML) algorithm was applied to design a signature associated with DED-MGD. RESULTS: Forty-five immune genes were found upregulated in DED-MGD vs. controls, involved in eight signaling pathways, IFN I/II, MHC class I/II, immunometabolism, B cell receptor, T Cell receptor, and T helper-17 (Th-17) differentiation. Additionally, statistically significant correlations were found between 31 genes and clinical characteristics of the disease such as lid margin or tear osmolarity (Pearson's r < 0.05). ML analysis using a recursive feature elimination (RFE) algorithm selected a 4-gene mRNA signature that discriminated DED-MGD from control samples with an area under the ROC curve (AUC ROC) of 0.86 and an accuracy of 77.5%. CONCLUSIONS: Multiplexed mRNA analysis of conjunctival cells can be used to analyze immune gene expression patterns in patients with DED-MGD and to generate diagnostic signatures.

Prospective evaluation of intense pulsed light treatment for meibomian gland dysfunction and blepharitis due to ocular rosacea

Background: Ocular rosacea is a common skin condition leading to dry eye that is difficult to manage. Objectives: To estimate the efficacy and safety of a new intense pulsed light device, Thermaeye Plus, for meibomian gland dysfunction and blepharitis due to ocular rosacea. Materials & Methods: This prospective, longitudinal study included 74 eyes of 37 consecutive patients with ocular rosacea, with mean age of 45.6±11.7 years. Four consecutive sessions were undertaken, including14 flashes with 10 J/cm² on the periocular area and facial cheeks on Day 1, 14, 28, and 49. Clinical evaluation was based on: ocular surface disease index (OSDI) and symptom score questionnaires, quality of live and facial severity degree, non-invasive tear meniscus height, non-invasive tear break up time, corneal fluorescein staining and eyelid margin and meibomian gland assessment. Adverse effects on the eye and periocular area, and systemic complications were evaluated. Results: The OSDI questionnaire showed a decrease in symptoms, achieving normal values in 91.9% of patients. The symptom score showed amelioration, with the most significant changes relating to dryness, foreign body sensation, light sensitivity, and pain. Longitudinal analysis showed the most significant improvement between baseline at Day 1 and 49. All eyelid signs improved, most significantly for telangiectasia/vascularity and blepharitis, leading to a 78% clearance of facial rosacea and 81.1% reduction of flushing. In total, 100% of the patients reported an improvement in their quality of life after treatment and 94.6% a very significant improvement (p<0.001). Conclusion: These results demonstrate that Thermaeye Plus is an effective and safe treatment for ocular rosacea.

Prospective evaluation of a new intense pulsed light, thermaeye plus, in the treatment of dry eye disease due to meibomian gland dysfunction.

PURPOSE: This study aims to estimate the efficacy and safety of a new intense pulsed light (IPL) Thermaeye Plus for dry eye disease (DED) secondary to meibomian gland dysfunction (MGD). PATIENTS AND METHODS: This is a prospective, longitudinal study of patients with moderate to severe MGD. Treatment consisted of 4 consecutive IPL sessions, 12 flashes with the same energy 8J/cm2 on the periocular area at days 1, 14, 28, and 49. All patients were evaluated before each IPL sessions and 1 and 4 months after the last session. Measuring: Symptoms score and OSDI questionnaire, Non-invasive tear meniscus height (NITMH), Non-invasive break up (NITBUT), Tear osmolarity (TO), Corneal fluorescein staining (CFS) and Eyelid margin and Meibomian gland assessment. The adverse effects on the eye, periocular area, and systemic complications were evaluated. All types of skin pigmentation (Fitzpatrick scale I to VI) were included. RESULTS: The study included 44 consecutive patients (88 eyes), 40 males and 48 females, with a mean age of 52.5±13.6 years, ranging from 22 to 78 years. Significant improvements were observed in single and total signs and symptoms. The most significant changes were observed in dryness, foreign body sensation (p<0.001), and pain (p<0.005). The OSDI questionnaire showed a significant decrease in total symptoms (p<0.003). The percentage of patients with a normal index <13, improved from 23.8% (10 patients) at baseline to 80.9% (34 patients) at last visit, after 23 weeks. Clinical sings also improved, more than 90%, stand out telangiectasia and blepharitis (p<0.002, and p<0.0005, respectively). No statistical differences between age (<40y, 40-60y, and >60y) and gender were observed. The clinical improvement began after the second and third week after the first IPL session, until the end of the IPL treatment (D49). After that, the results maintained stable until the last visit, after 11 weeks. No complications were reported locally, nor in the periocular area as well as systemically. CONCLUSION: Thermaeye Plus, a new IPL for ophthalmic use, is a safe and effective treatment in patients with DED due to MGD, showing improvement from the second week of treatment and maintaining until the last visit, 4 months after the last IPL session (23 weeks of total follow-up). Patients with pigmented skin (Fitzpatrick V or VI) have been treated with no side effects. It is relevant, especially to apply in brown-dark skin populations since complications with other IPL devices have been reported.

Accommodative intraocular lens tilting.

PURPOSE: To report an unusual complication of accommodative intraocular lens (IOL) implantation after clear lens extraction for hyperopia correction. DESIGN: Observational case report. METHOD: A 48-year-old woman underwent clear lens exchange for the correction of moderate hyperopia. A Crystalens Model AT-45 Accommodating Posterior Chamber IOL (AT-45 IOL) was implanted to allow optimal distance and near vision. At the 3-week follow-up appointment, she complained of monocular diplopia. Ocular examination showed an increased astigmatism, causing decreased visual acuity. Scheimpflug Pentacam Image and Wave Front Analysis supported the diagnosis of IOL tilting. RESULTS: IOL repositioning was unsuccessful because of fibrosis of the haptics. It was necessary to replace AT 45 IOL with a monofocal acrylic sulcus-fixated IOL. CONCLUSION: Control of capsular fibrosis should be a major concern, especially in this type of IOL. Accommodating IOL exchange appears to be a safe alternative to manage this complication.

Corneal endothelium evaluation after phacoemulsification with continuous anterior chamber infusion.

PURPOSE: To determine if the use of continuous anterior chamber infusion (CACI) during conventional phacoemulsification can damage the corneal structure by adding an additional hydrodynamic stress to the corneal endothelium intraoperatively and to use this option routinely in small-incision phacoemulsification to soften its learning curve. METHODS: We performed a prospective, interventional, case series of patients with cataract who underwent phacoemulsification. Patients were previously classified into 2 groups based on whether CACI was used (group 2) intraoperatively or not (group 1). Pachymetry and endothelial cell (EC) density were evaluated before and after surgery, and data were compared between the 2 groups. Eyes with values of EC density less than 1000 cells/mm or showing previous corneal structural alterations were excluded from the study. RESULTS: Sixty-seven eyes were included in our study from September 2002 to January 2003. Group 1 included 31 eyes (mean pachymetry 520.4 microm and EC density 2883), and group 2 included 36 eyes (mean pachymetry 519.0 and EC density 2627). Multivariate analysis of postoperative data following a multiple regression model showed an increase in pachymetry for both groups at 24 hours after surgery that progressively diminished until the last visit 4 weeks postoperatively, and no statistically significant differences were found between the groups. EC density displayed an abrupt loss for both groups, especially for group 2, that reached statistical significance at day 7 after surgery (P = 0.020). EC density experienced an increase for both groups in follow-up visits, and it was not statistically different at last postoperative control (P = 0.361). CONCLUSIONS: : The trend in modern cataract surgery is to reduce postoperative ocular trauma, and this can be achieved by small-incision phacoemulsification. But it requires a learning curve that we believe can be softened by using some surgical maneuvers such as continuous anterior chamber infusion, which minimizes the risk for anterior chamber collapse during the intervention. Comparing postoperative pachymetry and EC density between group 1 and 2, we found that the use of CACI does not add any additional damage to corneal structures because the initial statistically significant EC loss at day 7 postoperatively has a prompt recovery in subsequent visits, and then the EC loss remains similar in both groups. Transition from conventional to bimanual phacoemulsification can be simplified by using CACI, and it does not increase postoperative corneal damage.

Surgical strategies in patients with cataract and glaucoma.

PURPOSE OF REVIEW: This review analyzes the most relevant studies on current surgical strategies to treat glaucoma patients with cataracts. RECENT FINDINGS: No clear evidence has confirmed better results with trabeculectomy alone compared with phacotrabeculectomy. Recent studies have reported successful outcomes combining deep sclerectomy and two-site phacoemulsification. The phacoemulsification cataract extraction will not vary the intraocular pressure of patients with previous deep sclerectomy. Mitomycin C proved to be effective in maintaining lower pressure levels with the combined surgery technique; however, 5-fluorouracil did not show any improvement. Minimally invasive cataract surgery reduces surgical trauma, making it possible to obtain better results with combined surgery and previous glaucoma surgery. SUMMARY: The surgical strategy decision must be customized to every patient. Only filtering surgeries are recommended in glaucoma patients with incipient cataract. Combined surgical procedures are recommended for progressive or advanced glaucoma. Two-site phacotrabeculectomy with mitomycin C achieves better stabilized results; however, combined phacoemulsification with deep sclerectomy or viscocanalostomy achieves similar results with a lower rate of complications. These promising findings need more study to be confirmed.

Laser cataract surgery: technique and clinical results.

PURPOSE: To study the effectiveness of an erbium:YAG (Er:YAG) laser in removing nuclei of various densities. SETTING: University clinic. METHODS: This nonrandomized prospective clinical study included 147 consecutive cataractous eyes: Group 1 (n = 71) had conventional ultrasound, and Group 2 (n = 76) had surgery with the Er:YAG laser. The 2 groups were further classified by cataract density. Patients were examined 6 months postoperatively to evaluate surgical time, intraocular pressure (IOP), pachymetry, endothelial cell loss, and visual acuity. RESULTS: With ultrasound cataract surgery, there were no significant changes in IOP compared with the preoperative measurements. Laser treatment of 3+ and 4+ cataracts resulted in IOP increases of 12.6% and 18.2%, respectively, compared with 1+ and 2+ cataracts (P<.001). Slight endothelial cell losses occurred in all cases. With ultrasound, the mean decrease was 2.8%, and with laser surgery, the results were similar except for a significant decrease of 13.4% with 4+ cataracts. There was a correlation between pachymetry and surgical time when the trauma related to surgical time and hydrodynamic flow in the anterior chamber was assessed. With ultrasound, the visual acuity was similar with all types of cataract; with the laser, similar normal values were seen with 1+ and 2+ cataracts but decreased values were seen with 3+ cataracts and lower values with 4+ cataracts-0.43 compared to 0.84 best corrected visual acuity with same-density cataracts treated with ultrasound (P<.0005). Patients with 4+ cataracts treated with the laser developed more complications than those treated with ultrasound. CONCLUSIONS: The Er:YAG laser was as effective and reliable as ultrasound in removing soft and medium-density cataracts. With dense cataracts, the surgical length produced more trauma and complications during laser treatment than during ultrasound treatment.

Laser-assisted deep sclerectomy.

PURPOSE: To study the clinical effectiveness of deep sclerectomy using the erbium:YAG (Er:YAG) laser in patients with open-angle glaucoma (OAG). SETTING: Department of Ophthalmology, Institut Universitari Dexeus, Universitat Autonoma de Barcelona, Barcelona, Spain. METHODS: This nonrandomized prospective clinical study was performed in 46 consecutive eyes with OAG. Seventeen patients had not received any treatment for glaucoma. Eight had received 1 medication; 14, 2 medications; and 7, 3 medications. The mean duration of treatment was 18.3 months +/- 9.4 (SD). After mitomycin-C 0.02% was administered for 2 minutes, a superficial 4.0 mm x 4.0 mm scleral flap was created and a deep 3.0 mm x 3.0 mm scleral ablation was performed with the Er:YAG laser. Schlemm's canal was removed, and the cornea was dissected to Descemet's membrane until aqueous humor percolated. The scleral flap and conjunctiva were closed. Postoperative follow-up examinations were done at 1, 3, and 7 days, 2, 3, and 4 weeks, and then every 3 months up to 15 months. RESULTS: The mean preoperative intraocular pressure (IOP) was 28.3 +/- 6.1 mm Hg. The mean postoperative IOP was 14.1 +/- 3.5 mm Hg at 24 hours, 16.3 +/- 4.2 mm Hg at 3 months, and 15.3 +/- 2.7 mm Hg at 15 months (P <.001). There were no statistically significant differences in IOP by sex or age. There was a statistically significant difference between patients receiving no medication and those who received more than 2 medications and a treatment period longer than 1 year preoperatively (P <.006). The presence of a filtering bleb was associated with a longer period of decreased IOP (P <.007). The success rate (IOP < or =18 mm Hg without medication) was 93.47% at 1 month and 84.78% at 15 months. The number of complications was significantly lower than in previous reports of trabeculectomy. One patient lost 2 lines of visual acuity because of cystoid macular edema. CONCLUSIONS: Deep sclerectomy using the Er:YAG laser was safe and effective in eyes with OAG. More studies are needed to analyze the mechanism of lowering IOP.