Case report: Incidental MALT lymphoma of the left adrenal gland mimicking a metastatic spread within durvalumab maintenance treatment in inoperable stage III non-small cell lung cancer

Durvalumab after chemotherapy in non-operable stage III non-small cell lung cancer (NSCLC) is the standard of care worldwide. We present a patient with the incidental discovery of a unilateral MALT lymphoma of the adrenal gland and adrenalitis during durvalumab maintenance treatment detected by 18F-FDG-PET/CT. We assessed the clinical and histopathological findings, radiological examinations and overall treatment. Our work emphasizes the significance of considering other differential diagnoses and the importance of multidisciplinary treatment of the findings, especially within clinical trials

Morphological and Functional Aspects and Quality of Life in Patients with Achromatopsia

(1) Background: Achromatopsia is a rare disease of which the natural course and impact on life are still unknown to this date. We aimed to assess the morphological, functional characteristics, and quality of life in a large sample size of patients with achromatopsia. (2) A total of 94 achromats were included in this retrospective cohort study. Sixty-four were patients of the Department of Ophthalmology, Saarland University Medical Centre in Homburg/Saar, Germany, between 2008 and 2021. Thirty further participants with achromatopsia from the national support group were included using an online questionnaire, which is available under ‘Supplementary data’. Statistical analysis was performed using SPSS Version 25; (3) The 94 patients (37 males (39.4%) and 57 females (60.6%)) showed a mean age of 24.23 ± 18.53 years. Visual acuity was stable (SD ± 0.22 logMAR at 1.0 logMAR) over a time of observation from 2008 to 2021. Edge filter glasses were the most used optical aids, while enlarged reading glasses were the most used low vision aids. (4) Conclusions: Our findings give an insight into describing the natural process and the quality of life of achromatopsia. The results demonstrate that achromatopsia is a predominantly stationary disease. The individual prescription of edge filters and low-vision aids is essential following a personalised fitting

Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND/AIM:mmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT). PATIENTS AND METHOD:We retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0-40% vs. 41-100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated. RESULTS:Median OS was 14 months (range: 3-167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively. CONCLUSION:Assessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT

Keratin 12 mRNA expression could serve as an early corneal marker for limbal explant cultures

This investigation aimed to identify early corneal marker and conjunctival epithelial differentiation through transcriptional analysis of limbal explant cultures and study early differentiation patterns of known corneal and conjunctival differentiation markers. 2 mm punch biopsies of limbal region were obtained from 6 donors of the Lions Cornea Bank Saar-Lorloux/Trier-Westpfalz. Limbal explants were dissected into corneal and conjunctival biopsy sections. Biopsies were placed with epithelial side down into 12 Wells. As soon as the outgrowing cells had reached confluence, they were harvested. mRNA expression of corneal differentiation markers KRT12, KRT3, DSG1, PAX6, ADH7 and ALDH1A1, conjunctival markers KRT19, KRT13 and stem cell marker ABCG2 were measured via qPCR. KRT12 and PAX6 protein expressions were evaluated using Western Blot. Results suggested that KRT12 mRNA expression was significantly higher in outgrowing cells from the corneal side of the biopsies as in those from the conjunctival side (p = 0.0043). There was no significant difference in mRNA expression of other analyzed markers comparing with marker expression of outgrown cells from both limbal biopsies (p > 0.13). KRT12 and PAX6 Western Blot analysis showed no difference in cells harvested from both sides. In conclusion, KRT12 mRNA might be a marker to measure corneal origin of cells from limbal biopsies with unknown composition of corneal and conjunctival progenitor cells. KRT3, DSG1, PAX6, ADH7, ALDH1A1, KRT19, KRT13 and ABCG2 mRNA as well as KRT12 and PAX6 protein expression could not contribute to differentiate corneal from conjunctival cell identity from limbal biopsies

Visual Impairment and Low Vision Aids : A Comparison between Children and Adults

(1) Background: This study aims to highlight differences in the etiology and fitting of low vision aids in visually impaired children and adolescents in comparison to adults. (2) Methods: A retrospective data collection from visually impaired patients presenting to obtain assistive devices from 1 January 2016 to 30 April 2020 was conducted. A total of 502 patients were included. Inclusion criteria were a minimum age of 4 years and the chart notation of a best-corrected distance visual acuity in the patient record prior to the fitting of magnifying visual aids. (3) Results: Of the 502 patients, 147 (29.3%) were children under the age of 18 years. The most common cause of visual impairment in children was albinism, and in adults, it was age-related macular degeneration (AMD). Children showed better distance visual acuity, with a median of 0.88 logMAR (Logarithm of the Minimum Angle of Resolution) compared to 1.0 in adults (p = 0.001). Near visual acuity was also significantly better, with a median of 0.54 logMAR in children compared to 0.9 in adults (p < 0.001). Near and distance visual acuity were significantly improved by fitting magnifying visual aids (p < 0.001). After fitting, near visual acuity averaged 0.3 logMAR, and distance visual acuity, 0.7. The most commonly prescribed aids were optical vision aids, which 68.5% of the patients received; 43.8% received electronic aids. In children, optical aids were more frequently prescribed, and in adults, electronic and acoustic aids (p < 0.001). (4) Conclusion: Visually impaired patients can regain the ability to read and improve distance vision by using individually adapted and tested magnifying vision aids, often with optical aids alone. Differences between children and adults could be discovered in the etiology and severity of visual impairment, as well as in the provision type of low vision aids

A Novel Likely Pathogenic Variant in the BLOC1S5 Gene Associated with Hermansky-Pudlak Syndrome Type 11 and an Overview of Human BLOC-1 Deficiencies

Hermansky-Pudlak syndrome (HPS) is a heterogeneous disorder combining oculocutaneous albinism (OCA) and a platelet function disorder of varying severity as its most prominent features. The genes associated with HPS encode for different BLOC- (biogenesis of lysosome-related organelles complex) complexes and for the AP-3 (adaptor protein-3) complex, respectively. These proteins are involved in maturation, trafficking, and the function of lysosome-related organelles (LROs) such as melanosomes and platelet δ-granules. Some patients with different types of HPS can develop additional complications and symptoms like pulmonary fibrosis, granulomatous colitis, and immunodeficiency. A new type of HPS has recently been identified associated with genetic alterations in the BLOC1S5 gene, which encodes the subunit Muted of the BLOC-1 complex. Our aim was to unravel the genetic defect in two siblings with a suspected HPS diagnosis (because of OCA and bleeding symptoms) using next generation sequencing (NGS). Platelet functional analysis revealed reduced platelet aggregation after stimulation with ADP and a severe secretion defect in platelet δ-granules. NGS identified a novel homozygous essential splice site variant in the BLOC1S5 gene present in both affected siblings who are descendants of a consanguine marriage. The patients exhibited no additional symptoms. Our study confirms that pathogenic variants of BLOC1S5 cause the recently described HPS type 11

An attempt to optimize the outcome of penetrating keratoplasty in congenital aniridia-associated keratopathy (AAK)

Purpose To propose an optimized microsurgical and medical approach to reduce the risk of complications after penetrating keratoplasty (PKP) in patients with aniridia-associated keratopathy (AAK). Methods Retrospective observational case series of 25 PKP performed in 16 patients with AAK. Preoperative indications were endothelial decompensation and vascularized scars (68%) or graft failure (32%) due to limbal stem cell deficiency. The optimized approach included a combination of a small corneal graft size (around 7.0 mm), interrupted 10–0nylon sutures, simultaneous AMT as a patch, large bandage contact lens, temporary lateral tarsorrhaphy, postoperative autologous serum eye drops, and systemic immunosuppression. Main outcome measures included: visual acuity, transplant survival, and complications encountered during follow-up of 107 weeks on average. Results A complete modified keratoplasty scheme was used in 10 of 25 PKP (group 1), while at least one of the modifications was missing in the other 15 PKP (group 2). After 8 weeks of follow-up, the epithelium was closed in 23 eyes. Visual acuity improved in 19 eyes at 6 months of follow-up, and remained stable in six eyes. None of the eyes showed a decrease in visual acuity. At the last post-operative follow-up, this visual improvement persisted in 14 eyes and graft survival rate after 156 weeks (3 years) was 69% in group 1 versus 44% in group 2 (p = 0.39, log-rank test). Secondary corneal neovascularization (8%), scarring (4%), ulcer (4%), or graft rejection (8%) happened mostly in the second group which was missing at least one of the suggested modifications. Conclusions PKP in congenital aniridia must be considered as a high-risk keratoplasty. An optimized therapeutic approach seems to be promising in order to reduce the postoperative complication rate in these most difficult eyes

Topical NSAIDs and Oral Acetazolamide for Macular Edema after Uncomplicated Phacoemulsification : Outcome and Predictors of Non-Response

Purpose: To investigate the effectiveness of nonsteroidal anti-inflammatory eye drops (NSAIDs) combined with oral acetazolamide for postoperative macular edema (PME) after uncomplicated phacoemulsification (PE) and identify predictors of non-response. Methods: We analyzed data of uncomplicated PE and identified eyes with PME. First-line therapy included topical NSAIDs combined with oral acetazolamide. In the case of non-response, triamcinolone was administered subtenonally. Outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: 94 eyes out of 9750 uncomplicated PE developed PME, of which 60 eyes were included. Follow-ups occurred 6.4 ± 1.8, 12.5 ± 3.7 and 18.6 ± 6.0 weeks after diagnosis. BCVA and CMT improved significantly in all follow-ups. In total, 40 eyes showed a response to first-line therapy at the first follow-up (G1). The remaining 20 eyes showed no response and required subtenon triamcinolone (G2), of which 11 eyes showed complete regression at the second followup and 4 eyes at third follow-up. A further 5 eyes showed no response and required intravitreal injection. Multivariate linear regression model showed that Diabetes mellitus (DM) and increased cumulative dissipated energy (CDE) are predictors of non-response. Conclusion: Topical NSAIDs with acetazolamide resulted in complete regression of PME in 67% of all cases. DM and increased CDE might be considered as predictors of non-response to this treatment