Anterior chamber fibrin reaction during Descemet membrane endothelial keratoplasty.

PURPOSE: To report a series of five cases of intraoperative spontaneous anterior chamber fibrin reaction during Descemet Membrane Endothelial Keratoplasty (DMEK). METHODS: We retrospectively collected demographic data and data for ocular disease history for each patient. Donor age, preoperative graft endothelial density, surgical complications on surgery and intraoperative OCT videos, intraoperative management and outcome were assessed. The same standardized DMEK technique was used for all patients. RESULTS: We report intraoperative fibrin formation in five eyes subjected to DMEK. Three pseudophakic eyes underwent single DMEK, and the other two underwent combined DMEK and cataract surgery. In one case, a fibrin filament was observed before graft insertion, with multiplication during surgery, whereas, in the other four cases, strands of fibrin from the iris appeared after graft insertion. This complication resulted in graft failure in four cases (80%). No recipient- or donor-related risk factor was identified. CONCLUSIONS AND IMPORTANCE: The anterior chamber fibrin reaction is a very uncommon complication of DMEK. The underlying pathophysiological mechanisms remain unknown, but analyses of surgical videos and intraoperative OCT suggest iris involvement. This phenomenon may be induced by chronic subclinical anterior chamber inflammation, due to a blood-aqueous barrier breakdown associated with acute iris trauma during surgery. Thus, intraoperative microtraumatism of the iris should be avoided.

Tilted disc syndrome (TDS): New hypotheses for posterior segment complications and their implications in other retinal diseases.

Tilted disc syndrome (TDS) is considered a congenital anomaly due to a delayed closure of the embryonic fissure. It is characterized by an oblique orientation of the axis of the optic disc, associated with other posterior pole anomalies such as inferior crescent, situs inversus and inferior staphyloma. The aim of this review was to summarize the data supporting the current hypotheses for the pathogenesis of TDS, and its anatomical and functional clinical consequences. Recent imaging techniques, such as magnetic resonance imaging, wide-field fundus imaging, and 2- and 3-D optical coherence tomography have provided a new perspective on TDS and its complications. Different abnormalities have previously been reported, both in the anterior and posterior segments. The focus was on vision-threatening chorioretinal changes or complications, including choroidal neovascularization and serous retinal detachments and their therapeutic options. Based on clinical observations, assumptions were proposed to understand the occurrence of complications such as chorioretinal degenerative changes, choroidal neovascularization and polypoidal choroidal vasculopathy, macular serous retinal detachment, myopic foveoschisis and chorioretinal folds. These hypotheses could be referred to as the curvature "breaking point" hypothesis, the uneven growth "tractional" hypothesis, the "container-content" imbalance hypothesis, and the "choroidal funnel" hypothesis. Because these complications could also occur in other contexts, understanding the pathogenesis of TDS complications could help to understand their pathophysiology.

Assessing the correlation between swept-source optical coherence tomography lens density pattern analysis and best-corrected visual acuity in patients with cataracts.

OBJECTIVE: To assess linear correlation between swept-source optical coherence tomography (SS-OCT) lens density variation and patients' best-corrected visual acuity (BCVA). METHODS AND ANALYSIS: Linear densitometry was performed on horizontal lens images from 518 eyes, obtained using SS-OCT. All densities from the anterior to the posterior side of the cataract were exported for detailed analysis. The algorithm used a classical random forest regression machine learning approach with fourfold cross-validation, meaning four batches of data from 75% of the eyes with known preoperative best-corrected visual acuity (poBCVA) were used for training a model to predict the data from the remaining 25% of the eyes. The main judgement criterion was the ability of the algorithm to identify linear correlation between measured and predicted BCVA. RESULTS: A significant linear correlation between poBCVA and the algorithm's prediction was found, with Pearson correlation coefficient (R)=0.558 (95% CI: 0.496 to 0.615, p<0.001). Mean BCVA prediction error was 0.0965±0.059 logarithm of the minimal angle of resolution (logMAR), with 312 eyes (58%) having a BCVA prediction correct to ±0.1 logMAR. The best algorithm performances were achieved for 0.20 logMAR, with 79%±0.1 logMAR correct prediction. Mean, anterior cortex, nucleus and posterior cortex pixel density were all not correlated with patient BCVA. CONCLUSION: Pixel density variations based on axial lens images provided by SS-OCT biometer provide reasonably accurate information for machine learning analysis to estimate patient BCVA in all types of cataracts. This study demonstrates significant linear correlation between patients' poBCVA and the algorithmic prediction, with acceptable mean prediction error.

Corneal Remodeling After Myopic SMILE: An Optical Coherence Tomography and In Vivo Confocal Microscopy Study.

PURPOSE: To study corneal remodeling during the first 6 months after myopic small incision lenticule extraction (SMILE) with a 10% overcorrection nomogram, by spectral-domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM). METHODS: This prospective non-randomized observational study included 60 eyes from 30 patients treated by SMILE for low to moderate myopia. A 10% overcorrection nomogram was applied for all eyes. Epithelial and corneal thickness maps were obtained within the central 6 mm, by SD-OCT, at each visit. Lenticule thickness was calculated by subtracting the postoperative central stromal thickness from the preoperative central stromal thickness. IVCM was performed at each visit. RESULTS: The mean surgical refractive correction was -3.99 ± 1.50 diopters (D) before and -0.09 ± 0.37 D after surgery. Central epithelial thickness increased from 53.7 ± 4.0 to 57.1 ± 4.1 µm at 6 months after SMILE (P < .001). The measured lenticule thickness was 16 ± 6.1 µm less than the programmed lenticule thickness (P < .001). Both central epithelial hyperplasia and the mismatch between measured and programmed lenticule thickness were positively correlated to the degree of myopia (r2 = 0.60, P < .001 and r2 = 0.47, P < .001, respectively). Fibrosis at the interface was not correlated with epithelial thickening (r2 = 0.06, P = .29) or lenticule thickness error (r2 = 0.07, P = .22). CONCLUSIONS: Both epithelial thickening and the mismatch between the targeted and achieved lenticule thickness resulted in a slight undercorrection with a 10% overcorrection nomogram in low and moderate myopia. Fibrosis at the interface was not responsible for lenticule thickness error. Additional overcorrection is required to increase accuracy. [J Refract Surg. 2020;36(9):597-605.].

Early recovery of quality of vision and optical performance after refractive surgery: Small-incision lenticule extraction versus laser in situ keratomileusis.

PURPOSE: To assess the early time course of the visual function after small-incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). SETTING: Quinze-Vingts National Ophthalmology Hospital, Paris, France. DESIGN: Prospective case series. METHODS: Patients scheduled for bilateral small-incision lenticule extraction or LASIK were consecutively enrolled. In addition to standard refraction and visual acuity, contrast sensitivity, aberrometry, and patient-reported quality of vision and overall satisfaction were measured 1 day, 7 days, and 1 month postoperatively. RESULTS: Each group comprised 23 patients (46 eyes). The postoperative contrast sensitivity was better in the LASIK group at 1 day (P = .014) and 7 days (P = .001) but not at 1 month. No significant differences in visual acuity, efficacy, or safety were found between the 2 groups throughout the follow-up. The objective scatter index assessed by double-pass aberrometry was better after LASIK 1 day postoperatively (P = .036) but was not statistically different thereafter. The patient-reported quality of vision was significantly worse in the small-incision lenticule extraction group than in the LASIK group at 7 days (P = .010). Global satisfaction did not differ between groups throughout the study. Significant correlations were found between contrast sensitivity and aberrometry in both groups at all examinations. CONCLUSIONS: Targeted analysis of early quality of vision through objective and subjective methods suggested that compared with LASIK, a slight delay in corneal optical recovery after small-incision lenticule extraction might lead to reduced contrast sensitivity and specific patient-reported visual disturbance during the first postoperative week with no effect on overall patient satisfaction.

Impact of Dry Eye Disease on Vision Quality: An Optical Quality Analysis System Study.

PURPOSE: We evaluated the relationship between ocular surface clinical tests and quality of vision in patients with dry eye disease (DED). METHODS: In this study, 136 eyes of 72 dry eye patients were evaluated retrospectively using the ocular surface disease index (OSDI), measurement of tear film break-up time (TBUT), the Oxford score, Van Bijsterveld score, and Schirmer I test. Quality of vision was assessed with the optical quality analysis system (OQAS) using the objective scatter index (OSI) recorded over 20 seconds without blinking. Correlations between dry eye symptoms and signs, and OSI measurements were evaluated. RESULTS: The OSI and OSI standard deviation (OSI SD) were correlated with TBUT (r = -0.21, P = 0.013 and r = -0.18, P = 0.038, respectively), Oxford score (r = 0.31, P = 0.0002 and r = 0.18, P = 0.032, respectively), and the Van Bijsterveld score (r = 0.33, P = 0.0001 and r = 0.25, P = 0.003, respectively). The OSI also was correlated with the Schirmer test (r = -0.19, P = 0.025), OSDI (r = 0.17, P = 0.04), and the ocular symptoms subscale of the OSDI (r = 0.21, P = 0.01). OSI SD was correlated with the environmental triggers subscale of the OSDI (r = 0.21, P = 0.016). CONCLUSIONS: Quality of vision measured with the OQAS was correlated with dry eye symptoms and signs. The OQAS could be a useful tool to better evaluate visual function in patients with DED. TRANSLATIONAL RELEVANCE: The OQAS provides a better understanding of patient complaints about alteration of vision quality. It might be useful to integrate this objective system in severity assessments and follow-up of DED, especially for treatment evaluations.

Dry eye disease after refractive surgery: comparative outcomes of small incision lenticule extraction versus LASIK.

PURPOSE: To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye disease. DESIGN: Prospective, comparative, nonrandomized clinical study. PARTICIPANTS: Thirty patients scheduled for bilateral myopic SMILE and 30 age-, sex-, and refraction-matched patients scheduled for bilateral myopic LASIK were enrolled and followed for 6 months after the surgery. METHODS: Complete evaluation of dry eye disease was performed at 1 and 6 months postoperatively, which included vision-related quality of life (Ocular Surface Disease Index [OSDI]), clinical examinations (tear film breakup time [TBUT], Schirmer I test, corneal staining), and tear osmolarity measurements, together with an overall severity score. Function and morphology of the corneal innervation were evaluated by corneal esthesiometry and subbasal nerve imaging using in vivo confocal microscopy (IVCM). MAIN OUTCOME MEASURES: Overall analysis of dry eye disease and corneal innervation. RESULTS: High incidence of mild to moderate dry eye disease was observed in both groups 1 month postoperatively, which remained significantly higher in the LASIK group than in the SMILE group 6 months after surgery (overall severity score [0-4]: 1.2±1.1 vs. 0.2±0.4, respectively, P < 0.01), leading to more frequent use of tear substitutes over the long term. Corneal sensitivity was better in SMILE than in LASIK eyes 1 month postoperatively (3.5±1.79 vs. 2.45±2.48, respectively, P < 0.01) and then recovered to statistically similar values at 6 months. Corneal nerve density, number of long fibers, and branchings as assessed by IVCM were significantly higher in the SMILE group compared with the LASIK group 1 and 6 months after surgery. Corneal sensitivity was negatively correlated with dry eye-related corneal damage (R² = 0.48, P < 0.01), and the long fiber nerve density was independently correlated with the OSDI score (R² = 0.50, P < 0.01) and the Schirmer test (R² = 0.21, P < 0.01) 6 months postoperatively. CONCLUSIONS: The SMILE procedure has a less pronounced impact on the ocular surface and corneal innervation compared with LASIK, further reducing the incidence of dry eye disease and subsequent degradation in quality of life after refractive surgery.

Clinical features, treatment methods, and evolution of birdshot chorioretinopathy in 5 different families.

PURPOSE: To report familial cases of birdshot chorioretinopathy (BSCR). DESIGN: Retrospective, observational case series. METHODS: Five families with 2 members in each (10 patients) with BSCR were included in this case series from a cohort of 225 patients followed up for BSCR. A review of medical and angiographic records of familial cases of BSCR was performed. We described and compared in each family the histocompatibility leukocyte antigen (HLA) typing, age at onset, ethnic group, clinical features, fluorescein and indocyanine green angiography results, evolution of disease, and treatment used with efficiency. RESULTS: HLA-A29 and HLA-B44 results were positive in 100% of patients tested. Mean age at onset was 46.5 years. All patients were White. Corticosteroids were required in 7 patients, and 3 patients had no treatment because of mild or moderate lesions. Cyclosporine A was administered in 2 patients from the same family. Period of follow-up ranged from 1 to 32 years (median, 7 years). CONCLUSIONS: Familial forms of BSCR remain rare and do not justify systematic examination in relatives of patients with BSCR.

Th1- and Th2-related chemokine and chemokine receptor expression on the ocular surface in endotoxin-induced uveitis.

PURPOSE: To determine whether the ocular surface inflammation in uveitis mimics or counteracts intraocular inflammatory pathways by directly comparing T-helper (Th) lymphocytes Th1 and Th2 markers in conjunctival and ciliary body expression in endotoxin-induced uveitis (EIU). This study used the following inflammatory markers: chemokine receptor, CC chemokine receptor 4 (CCR4), and its ligand, macrophage-derived chemokine (MDC), to evaluate Th2 participation; chemokine receptor, CCR5, to evaluate the Th1 system; and its ligand, regulated on activation normal T cell expressed and secreted (RANTES), to evaluate both Th1 and Th2 systems. METHODS: Immunohistochemistry and real-time polymerase chain reaction (RT-PCR) were used to compare protein and RNA expression of CCR4, MDC, CCR5, and RANTES in the conjunctiva and ciliary body in EIU 6 h and 24 h after the lipopolysaccharide (LPS) injection and in control (without injection) Lewis rats. RESULTS: Immunohistochemistry with CCR5, RANTES, and MDC showed an increase in fluorescent staining in the conjunctiva and ciliary body in the rats with uveitis compared to the control rats. For CCR4, immunostaining was comparable in the conjunctiva and ciliary body and did not show any clear differences between control rats and rats with EIU. For RANTES, MDC, and CCR5, RT-PCR showed a significantly higher RNA expression in conjunctiva and in ciliary body at 6 h compared to 24 h and controls. For CCR4, RT-PCR did not illustrate any significant differences in conjunctiva and in ciliary body between all groups of animals. CONCLUSIONS: Protein and RNA expressions of RANTES, MDC, and CCR5 were higher in EIU rats than in control rats in the conjunctiva and ciliary body whereas the CCR4 level was not modified in the conjunctiva and ciliary body of EIU rats when compared to controls. Th1 activation seemed to predominate in this model with high levels of CCR5 expression and no increased expression of CCR4, but Th2 participation with MDC was noted. The expression of RANTES, MDC, CCR4 and CCR5 in EIU was quite similar between the conjunctiva and the ciliary body, so conjunctival inflammation might reproduce the intraocular inflammation, probably generated by local extension and diffusion in this model. If the ocular surface mimics intraocular inflammatory pathways, the conjunctiva may provide a new and easier access for uveitis studies.

The corneal endothelium in an endotoxin-induced uveitis model: correlation between in vivo confocal microscopy and immunohistochemistry.

PURPOSE: To analyze the involvement of the corneal endothelium in uveitis to better understand the formation mechanisms and the keratic precipitate composition. In vivo confocal microscopy images were correlated with ex vivo immunostaining of corneal endothelium from rat eyes with endotoxin-induced uveitis (EIU). METHODS: EIU was induced in Lewis rats by lipopolysaccharide (LPS) injection. Slit-lamp examination and in vivo confocal microscopy were performed 6, 24, 48, 72, and 96 h after the LPS injection. One group of rats was killed at 24 h and the other rats at 96 h. Immunohistochemistry on corneal endothelium using antibodies to intercellular adhesion molecule (ICAM-1), phalloidin, CD68 (anti-macrophage), MCA967 (anti-granulocyte), T cell receptor alpha/beta (TCR alpha/beta; anti-lymphocyte), zonula occludens-1 (ZO-1), and occludin was performed on flat-mount corneas and was analyzed using a three dimensional (3D) laser confocal microscope. RESULTS: In vivo confocal microscopy showed numerous hyperreflective round dots on the corneal endothelium, in the anterior chamber, and in the anterior stroma corresponding to inflammatory cells with a maximum at 24 h after the injection and detectable until the 96th hour. Upon immunostaining, corneal endothelial cells in rats with EIU overexpressed ICAM-1. ZO-1 and occludin had a lower endothelial expression and more heterogeneous distribution in EIU rats than in controls, showing disruption of endothelial cell junctions. Compared to controls, CD68, MCA967, and TCR alpha/beta expression was observed in corneas in rats with EIU. The two techniques showed a circular peripheral network of corneal vessels derived from a large circumferential vascular structure resembling the major arterial circle of iris where the inflammatory cells marginalized to infiltrate the anterior stroma. CONCLUSIONS: The correlation between in vivo confocal microscopy and ex vivo immunostaining helped to better understand in vivo confocal microscopy images. The two new techniques applied here were very effective and complementary in evaluating the corneal endothelium involvement in EIU. Based on these findings, in vivo confocal microscopy in clinical practice could be very helpful to better analyze keratic precipitates and corneal modifications in patients with uveitis.

Th1 and Th2 responses on the ocular surface in uveitis identified by CCR4 and CCR5 conjunctival expression.

PURPOSE: To investigate CC chemokine receptor 4 (CCR4) and CC chemokine receptor 5 (CCR5) expression, known to be related to the Th2 and Th1 inflammatory pathways, respectively, and human leukocyte antigen-D related (HLA-DR) antigens as hallmarks for ocular surface inflammation in patients with uveitis using conjunctival impression cytologic specimens. DESIGN: Case-controlled study. METHODS: Conjunctival impression cytologic specimens were obtained from patients with anterior uveitis (n = 26), and their inflammatory profile was compared with those of patients with vernal keratoconjunctivitis (VKC; n = 24), keratoconjunctivitis sicca (KCS; n = 17), and normal subjects (n = 17). Expressions of CCR4, CCR5, and HLA-DR were analyzed using flow cytometry and were expressed by determining the percentage of cells expressing the markers in the conjunctival epithelium. RESULTS: CCR4 was overexpressed in the uveitis group (mean, 19.8% +/- 19.7% of positive cells) and in the VKC group (24.7% +/- 20.1%). CCR5 was expressed only weakly in uveitis patients (6.4% +/- 13.1%) and in the normal subjects (2.4% +/- 2.4%). HLA-DR expression by conjunctival cells was increased in the uveitis patients (57.4% +/- 21.1%) and in the KCS group (52.4% +/- 12.1%) compared with the VKC group (23.9% +/- 26.8%; P < .001) and normal subjects (22.1% +/- 19.1%; P < .001). CONCLUSIONS: CCR4, classically related to the Th2 system, and HLA-DR both were overexpressed by the conjunctival epithelium in uveitis patients, whereas CCR5, related to the Th1 system, was expressed weakly in uveitis patients. These preliminary results seem to suggest an involvement of the Th2 system on the ocular surface in uveitis. Exploration of the ocular surface in uveitis may represent a new way to understand better the immune pathways involved in this complex disease.