Effector T Cells Promote Fibrosis in Corneal Transplantation Failure.

Purpose: To evaluate whether fibrosis contributes to corneal transplant failure and to determine whether effector CD4+ T cells, the key immune cells in corneal transplant rejection, play a direct role in fibrosis formation. Methods: Allogeneic corneal transplantation was performed in mice. Graft opacity was evaluated by slit-lamp biomicroscopy, and fibrosis was assessed by in vivo confocal microscopy. Expression of alpha-smooth muscle actin (α-SMA) in both accepted and failed grafts was assessed by real-time PCR and immunohistochemistry. Frequencies of graft-infiltrating CD4+ T cells, neutrophils, and macrophages were assessed using flow cytometry. In vitro, MK/T-1 corneal fibroblasts were co-cultured with activated CD4+CD25- effector T cells isolated from corneal transplant recipient mice, and α-SMA expression was quantified by real-time PCR and ELISA. Neutralizing antibody was used to evaluate the role of interferon gamma (IFN-γ) in promoting α-SMA expression. Results: The majority of failed grafts demonstrated clinical signs of fibrosis which became most evident at week 6 after corneal transplantation. Failed grafts showed higher expression of α-SMA as compared to accepted grafts. Flow cytometry analysis showed a significant increase in CD4+ T cells in failed grafts compared to accepted grafts. Co-culture of activated CD4+CD25- effector T cells with corneal fibroblasts led to an increase in α-SMA expression by fibroblasts. Inhibition of IFN-γ in culture significantly suppressed this increase in α-SMA expression as compared to immunoglobulin G control. Conclusions: Fibrosis contributes to graft opacity in corneal transplant failure and is mediated at least in part by effector CD4+ T cells via IFN-γ.

Visual results and subjective satisfaction after implantation of two different trifocal diffractive intraocular lenses models (AcrySof IQ PanOptix and AT LISA tri 839 MP).

BACKGROUND: This study aimed to compare visual results following the implantation of two distinct diffractive trifocal IOLs utilizing various vision evaluation techniques and subjective satisfaction. METHODS: The study included 32 eyes receiving AcrySof IQ PanOptix implantation and 32 receiving AT LISA tri 839 MP. Post-operative examination at one year included uncorrected visual acuity (UCVA), distance-corrected visual acuity (DCVA) at 4 m, 80 cm, 60 cm, and 40 cm, Contrast sensitivity under photopic and mesopic conditions, and a questionnaire on subjective quality of vision, optical phenomena, and spectacle independence. RESULTS: The two groups were similar in baseline demographics, pre-operative visual, biometric data (except for axial length), and surgical paraments. The PanOptix outperformed the AT LISA tri in the intermediate range when using the standard visual acuity testing (UCVA: 0.23 ± 0.14 logMAR vs. 0.31 ± 0.17 logMAR, p = 0.04; BCVA: 0.21 ± 0.12 vs. 0.28 ± 0.14, p = 0.03) and in the intermediate and far range when using the interactive computer program (intermediate: UNVA "E" optotype test: 0.05 ± 0.12 vs. 0.12 ± 0.13, p = 0.03; Far: UNVA "E" optotype: 0.07 ± 0.12 vs. 0.13 ± 0.10, p = 0.05). In addition, the PanOptix group had higher contrast sensitivity under photopic and mesopic conditions with and without glare at all spatial frequencies. There was no difference in subjective outcomes between the groups. CONCLUSIONS: Patients who received PanOptix IOL had better visual outcomes for intermediate and far with higher contrast sensitivity under various conditions. Based on patients ' needs and demands, these results could support discussion when tailoring the optimal multifocal IOl.

Is Demodex Blepharitis Connected With Cataract Surgery?

PURPOSE: To determine whether there is an increased incidence of Demodex of the eyelashes among patients after cataract extraction surgery. DESIGN: Prospective, noncomparative clinical study. METHODS: A cohort of patients who underwent cataract extraction surgery had several eyelashes removed preoperatively that were examined independently by the hospital laboratory for the presence of the Demodex mite. This was repeated 3 weeks after surgery. During several postoperative weeks, patients received the standard treatment of steroid drops alone for a period as individually required. RESULTS: A total of 62 patients were included in the study (31 men and 31 women), with a mean age of 71.04 years (range, 47-87). In the group positive for Demodex, the male-to-female ratio was 2:3 (P = .2772). Demodex colonization was observed in 22.58% of samples before cataract surgery and in 32.26% after cataract surgery and topical postoperative steroid therapy (P = .0143). CONCLUSIONS: There is a statistically significant increase in Demodex colonization of eyelashes after cataract surgery and postoperative topical steroid treatment. Although Demodex colonization does not necessarily cause blepharitis, our findings of increased colonization should raise the possibility of Demodex blepharitis being considered by ophthalmologists in patients with chronic postoperative eye discomfort after cataract surgery. This study was carried out at the Emek Medical Center.

Differences in retinal images quality between normal and subclinical keratoconus and its association to posterior corneal asymmetry.

PURPOSE: To compare retinal image quality in subclinical keratoconus and normal eyes using a double-pass aberrometer and to correlate it with posterior surface deformation. METHODS: Sixty normal corneas were compared to 20 subclinical keratoconus (SKC) corneas. Retinal image quality was assessed using a double-pass system in all the eyes. The objective scatter index (OSI) modulation transfer function (MTF) cutoff, Strehl ratio (SR), and Predicted Visual Acuity (PVA) values at 100%, 20%, and 9% were calculated and compared between the groups. Posterior corneal asymmetry was measured using a combined Placido Dual Scheimpflug Analyzer, and correlations were tested with all optical quality parameters. RESULTS: Significant decrease in optical quality parameters was observed in SKC eyes compared with that in normal eyes. Subclinical KC eyes expressed greater scattering (OSI = 0.66 ± 0.36 vs 0.47 ± 0.26) and reduced contrast images (MTF and SR) than normal eyes, with 38.82 ± 9.4 and 0.22 ± 0.04, and 44.35 ± 7.1 and 0.24 ± 0.04, respectively. The reduction in the image contrast parameters (MTF and SR) was strongly correlated to the level of posterior corneal asymmetry in SKC. The greater the posterior asymmetry, the more affected was the image contrast, with r = -0.63 and -0.59, respectively for MTF and SR. CONCLUSION: Retinal image quality was significantly more affected in eyes with subclinical keratoconus than in normal eyes. The reduction in optical quality observed in subclinical keratoconus was strongly associated with the increased asymmetry of the posterior cornea.

SYRINGE DESIGN AND FILLING TECHNIQUE AFFECT ACCURACY OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INTRAVITREAL INJECTIONS.

PURPOSE: To evaluate the effect of syringe design and filling technique on the accuracy of anti-vascular endothelial growth factor delivery. METHODS: Volume output was measured with three syringe designs: a 1.0-mL slip-tip syringe, a 1.0-mL Luer-lock syringe, and a ranibizumab prefilled syringe-using two filling techniques ("upward" and "downward") and two fluids (water and bevacizumab). A total of 300 simulated injections were performed. Accuracy was determined by difference from the intended volume of 50 µ L and by mean absolute percentage error. RESULTS: Volume outputs were significantly different between syringe designs, with mean values of 61.99 ± 4.18 µ L with the 1-mL slip-tip syringe, 57.43 ± 4.95 µ L with the Luer-lock 1-mL syringe, and 51.06 ± 4.74 µ L with the ranibizumab syringe, making the latter the most accurate syringe. There were 37 cases (12.3%) of underdosing below 50 µ L, the majority of which occurred with the ranibizumab syringe. The "downward" technique reduced the occurrence of air bubbles. CONCLUSION: Intravitreal injections using 1.0-mL syringes are less accurate than using the ranibizumab prefilled syringe, which has a low-volume and low dead-space plunger design. The variability in volume output may result in less predictable treatment response, especially in cases of underdosing, which were more common with the ranibizumab syringe.

Real-world experience with belantamab mafodotin therapy for relapsed/refractory multiple myeloma: A multicentre retrospective study.

Belantamab mafodotin, an immuno-conjugate targeting B-cell maturation antigen, showed single-agent activity in phase 1 and 2 studies, and was recently approved for heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. Real-world data and long-term follow-up are scarce. We conducted a multisite retrospective study aimed to assess safety and efficacy of belantamab mafodotin monotherapy administered via the GSK expanded access compassionate care programme. One-hundred and six RRMM patients were treated with belantamab mafodotin between July 2019 and March 2021. The median age was 69.4 years. Patients were heavily pretreated with a median of six (range 2-11) prior therapy lines. Major adverse effects included ocular toxicity (keratopathy 68.4%, grade ≥3: 40.5%; blurred vision 36.8%, grade ≥3: 6.3%), thrombocytopenia (27.4%, grade ≥3: 17.9%) and infections (11.3%, grade ≥3: 7.5%). Median follow-up time was 11.9 [95% confidence interval (CI) 10.0-13.8] months. Overall response rate was 45.5%. Median progression-free survival was 4.7 (95% CI 3.5-5.9) months in the entire cohort and 8.8 (95% CI 6.6-10.9) months among responders. Median overall survival was 14.5 (95% CI 9.5-19.6) months, and not reached for responders. To conclude, in a real-world setting, belantamab mafodotin monotherapy showed efficacy comparable with the prospective clinical trials, with a tolerable toxicity profile.

Intravitreal air bubbles following intravitreal injections: a comprehensive analysis.

PURPOSE: To evaluate the prevalence of residual air bubbles following intravitreal injections of anti-VEGF agents, and to compare two techniques designed to reduce their occurrence. METHODS: Patients who received intravitreal injections reported the presence of air bubbles following the procedure, and were followed to determine when they disappeared. Two techniques used to reduce air bubbles prior to injection were compared-tapping the syringe with the needle up ("upwards" technique) or down ("downwards" technique). Rates of residual air bubbles were compared between techniques, and between different drugs. RESULTS: The study included 344 intravitreal injections, 172 injected with each technique. The overall rate of residual air bubbles was 11.3%, with 94.9% resolution by 48 h. The rate was significantly lower with the "downwards" technique (7.5% vs. 15.1%, p = 0.027). It was also significantly lower with ranibizumab injected using pre-filled syringes than with bevacizumab and aflibercept (0% vs. 12.1% and 14.7%, p < 0.0001). A questionnaire revealed patients reported medium levels of discomfort and a high importance of avoiding air bubbles. CONCLUSIONS: Residual air bubbles are a common occurrence, likely to be experienced by most patients undergoing repeated injections. This phenomenon may be significantly reduced by using the described "downwards" technique, or pre-filled syringes.

The 100 Most Cited Articles on Vitrectomy: A Bibliographic Perspective.

PURPOSE: To analyze the 100 most-cited articles on pars plana vitrectomy (PPV). DESIGN: Bibliographic study. METHODS: Literature search using the bibliographic databases of the ISI Web of Knowledge, limited to research articles published between 1971 and 2018 in peer-reviewed journals of ophthalmology. MAIN OUTCOME MEASURE: Number of citations since publication. RESULTS: The 100 most-cited articles on PPV were published in 11 different ophthalmology journals, with 73 of them published in Ophthalmology (n = 31), American Journal of Ophthalmology (n = 26), and Archives of Ophthalmology (n = 16). They originated from 14 different countries, predominantly from the United States (n = 64), and 99 of them were written in English. Their topics cover a wide spectrum of retinal conditions that vary from decade to decade as the technique of PPV evolved and became applicable to more indications. CONCLUSIONS: This bibliographic study provides a unique historic perspective of the development of PPV and its applications from its introduction to its current status.

Distinguishing Highly Asymmetric Keratoconus Eyes Using Dual Scheimpflug/Placido Analysis.

PURPOSE: To identify the best metrics or combination of metrics that provide the highest predictive power between normal eyes and the clinically unaffected eye of patients with highly asymmetric keratoconus using data from a Dual Scheimpflug/Placido device. DESIGN: Retrospective case-control study. METHODS: Combined Dual Scheimpflug/Placido imaging was obtained from the Galilei G4 device (Ziemer Ophthalmic Systems AG, Port, Switzerland) in 31 clinically unaffected eyes with highly asymmetric keratoconus and 178 eyes from 178 patients with bilaterally normal corneal examinations that underwent uneventful LASIK with at least 1 year follow-up. Receiver operating characteristic (ROC) curves were generated to determine area under the curve (AUC), sensitivity, and specificity for 87 metrics, and logistic regression modeling was used to determine optimal variable combinations. RESULTS: No individual metric achieved an AUC greater than 0.79. A combined model consisting of 9 metrics yielded an AUC of 0.96, with 90.3% sensitivity and 92.6% specificity. Among those 9 metrics included, 5 related to corneal pachymetry: Opposite Sector Index and Anterior Height BFS Z from the anterior surface, Asphericity and Asymmetry Index, Posterior Height BFS Z, and Posterior Height BFS X from the posterior surface. The strongest variable in the model was the thinnest point location on the horizontal (x) axis. CONCLUSION: While individual metrics performed poorly, using a combination of metrics from the combined Dual Scheimpflug/Placido device provided a useful model for differentiating normal corneas from the clinically normal eyes of patients with highly asymmetric keratoconus. Pachymetry values were the most impactful metrics.

Corneal Blood Staining after Complicated Cataract Surgery.

PURPOSE: To report the case of a patient with corneal blood staining after a complicated cataract surgery. OBSERVATIONS: We report on a 68-year-old woman who developed corneal blood staining secondary to hyphema after cataract surgery, despite the fact that intraocular pressure was not increased for a prolonged time. The corneal staining spontaneously cleared from the periphery towards the center. It was fully resolved after 2.5 years of follow-up. CONCLUSIONS AND IMPORTANCE: In case of hyphema induced by cataract surgery, performance of early anterior chamber washout should be considered to prevent corneal blood staining and poor visual outcome.

Differences in Posterior Corneal Features Between Normal Corneas and Subclinical Keratoconus.

PURPOSE: To compare posterior corneal features and their discriminating power for differentiating normal corneas from subclinical keratoconus using the Placido dual-Scheimpflug analyzer. METHODS: Patients were retrospectively included in the study. The preoperative normal right eyes of 79 patients imaged with a Placido dual-Scheimpflug system and with a stable postoperative LASIK follow-up of a minimum of 36 months were included in the normal group and were compared to 39 contralateral topographically normal eyes with clinically evident keratoconus in the fellow eye. The posterior surface variables measured were categorized according to the feature of the corneal shape they were characterizing (curvature, elevation, asymmetry, and eccentricity) and compared between the two groups using the Student's two-sample t test. The discriminating ability of the posterior surface variables was compared by receiver operator characteristics curves. RESULTS: Variables that related to asymmetry and elevation of the posterior surface were statistically significantly different between groups (P < .05), whereas eccentricity and curvature-related parameters were not. Receiver operator characteristics curves analysis showed that the maximum posterior elevation over the best-fit toric and aspheric surface reference shape had the highest discriminating ability for distinguishing normal corneas from subclinical keratoconus, with an area under the curve of 0.877, followed by the asphericity asymmetry index, with an area under the curve of 0.871, and posterior inferior-superior value, with an area under the curve of 0.851. CONCLUSIONS: Posterior cornea measured with a dual-Scheimpflug analyzer provides useful parameters for differentiating normal corneas from subclinical keratoconus. Of the posterior surface parameters, asymmetry and elevation seem to be the most sensitive shape modifications for differentiating both populations. [J Refract Surg. 2018;34(10):664-670.].

Publication outcome of abstracts submitted to the American Academy of Ophthalmology meeting.

OBJECTIVE: Abstracts submitted to meetings are subject to less rigorous peer review than full-text manuscripts. This study aimed to explore the publication outcome of abstracts presented at the American Academy of Ophthalmology (AAO) annual meeting. METHODS: Abstracts presented at the 2008 AAO meeting were analyzed. Each presented abstract was sought via PubMed to identify if it had been published as a full-text manuscript. The publication outcome, journal impact factor (IF), and time to publication were recorded. RESULTS: A total of 690 abstracts were reviewed, of which 39.1% were subsequently published. They were published in journals with a median IF of 2.9 (range 0-7.2) and a median publication time of 426 days (range 0-2,133 days). A quarter were published in the journal Ophthalmology, with a shorter time to publication (median 282 vs. 534 days, p=0.003). Oral presentations were more likely to be published than poster presentations (57.8% vs. 35.9%, p<0.001) and in journals with higher IFs (3.2 vs. 2.8, p=0.02). Abstracts describing rare diseases had higher publication rates (49.4% vs. 38.0%, p=0.04) and were published in higher IF journals (3.7 vs. 2.9, p=0.03), within a shorter period of time (358 vs. 428 days, p=0.03). In multivariate analysis, affiliation with an institute located in the United States (p=0.002), abstracts describing rare diseases (p=0.03), and funded studies (p=0.03) were associated with publication in higher IF journals. CONCLUSIONS: Almost 40% of abstracts were published. Factors that correlated with publication in journals with higher IF were a focus on rare diseases, affiliation with a US institute, and funding.

Extraocular muscle damage from dental implant penetration to the orbit.

PURPOSE: To demonstrate an unusual case of orbital trauma due to dental surgery complication. OBSERVATIONS: An elderly patient who underwent dental implantation to the zygomatic bone was hospitalized in the ophthalmology department with impaired abduction of her right eye, also evident on ocular examination. Head computed tomography demonstrated damage to the lateral rectus and to the inferior oblique muscles. Clinical assessment determined these muscles could not be repaired and reattached. The extent of irreversible damage in the patient was permanent limitation in movement of her affected eye with subsequent strabismus. CONCLUSIONS AND IMPORTANCE: Accurate pre-operative planning of dental zygomatic implant insertion, as well as selecting the size and direction of the implant, are imperative. Moreover, performing surgery in multidisciplinary centers with oculofacial plastic surgeons in such cases, may reduce risk of this complication, make it a safer procedure, and allow immediate treatment when required.

Positive Results Bias and Impact Factor in Ophthalmology.

PURPOSE: Previous studies in several fields of medicine have reported an association between the result of a trial (positive versus negative) and the impact factor of the journal in which it is published. The purpose of this study was to test the hypotheses that in the field of ophthalmology: (1) studies with positive results have a greater chance of being published in journals with a higher impact factor; (2) likewise, studies with a larger number of participants are more likely to be published in journals with a higher impact factor. METHODS: In this retrospective study, consecutive randomized, controlled trials conducted in the field of ophthalmology between 1 January 2010 and 1 January 2013 were retrieved from PubMed. Each study was classified as having either a positive or negative result. A positive result was defined as a study in which there was a statistically significant difference between groups (p < 0.05). The impact factor of the journal in which the study was published was retrieved. The number of patients enrolled and whether or not the trial was placebo controlled was documented as well. RESULTS: Out of 2524 studies identified, 892 met the inclusion criteria. Studies with positive results were published in journals with a significantly higher impact factor than that of the journals in which negative result studies were published (p < 0.001). Studies with positive results had a slightly larger number of participants than studies with negative results (p = 0.028). In multiple regression analysis, the ranked impact factor was significantly predicted by the primary outcome (positive versus negative results) and the number of participants in a study (total R(2 )= 2.95, p < 0.001). CONCLUSIONS: In the field of ophthalmology, articles with positive results are currently published in journals with a higher impact factor. This finding supports the ongoing occurrence of positive results bias in the field of ophthalmology.

Bmp5/7 in concert with the mid-hindbrain organizer control development of noradrenergic locus coeruleus neurons.

The locus coeruleus (LC) which is the major noradrenergic nucleus in the brain develops under the influence of Bmps secreted by the roof plate and Fgf8 emitted from the mid-hindbrain organizer. We studied the development of the LC in different Bmp mouse mutants and report the absence of this nucleus in Bmp5(-/-);Bmp7(-/-) double knockouts. Notably, genes marking organizers and neuronal populations adjacent to the LC precursor field are unperturbed in Bmp5(-/-);Bmp7(-/-) animals. In addition, we found that in En1(+/Otx2) mutants in which the caudal Otx2 expression domain and thereby the mid-hindbrain organizer are shifted caudally, LC neurons are concomitantly reduced along with Bmp5/7. Complementing these results, Otx1(-/-);Otx2(+/-) mutants, in which the mid-hinbrain organizer is shifted rostrally, show a rostrally extended Bmp5 expression area and an increase in LC neurons. Taken together, our data indicate that LC development requires either Bmp5 or Bmp7, and one is able to compensate for the loss of the other. In addition, we conclude that the position of the mid-hindbrain organizer determines the size of the LC and propose that Bmp5/7 play an important role in mediating this organizer function.