ESASO classification relevance in the diagnosis and evolution in diabetic macular edema patients after dexamethasone implant treatment.

PURPOSE: To assess the clinical relevance of The European School for Advanced Studies in Ophthalmology (ESASO) classification in patients with diabetic macular edema (DME) after their first dexamethasone implant (DEXI) treatment. METHODS: Retrospective real-world study conducted on consecutive DME patients who underwent DEXI treatment and were controlled at month-2. Subjects were initially classified according to the ESASO classification stages. The outcomes were anatomical biomarkers with spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). RESULTS: A total of 128 patients were classified according to ESASO classification stages as early (7; 5.5%), advanced (100; 78.1%), and severe (21; 16.4%). At baseline, there were significant differences between stages in BCVA, central macular thickness (CMT), and tomography anatomical biomarkers (p < 0.05). Initial BCVA (logMAR) was 0.33 ± 0.10, 0.58 ± 0.34, and 0.71 ± 0.35 in the early, advanced, and severe stages, respectively (p < 0.05). At month-2, BCVA was 0.17 ± 0.15, 0.46 ± 0.29, and 0.69 ± 0.27 in those classified as early, advanced, and severe stages, respectively. At month-2, DME was resolved or improved in 6 (85.7%), 60 (60%), and 12 (60%) patients classified as early, advanced, and severe stages, respectively. CONCLUSIONS: There was a good correlation between BCVA and ESASO classification stages. Patients in the severe stage did not achieve visual acuity improvement over the study period.

Acute dacryoadenitis in a patient with SARS-CoV-2 infection.

We describe a retrospective case report of dacryoadenitis associated with orbital inflammatory disease in a patient with confirmed SARS-CoV-2 infection.A 22-year-old previously fit and healthy male presented with 4-day history of right ocular redness, eyelid swelling and blurred vision associated with discomfort and pain in the lacrimal gland area. He was found to have right acute dacryoadenitis based on clinical examination and orbital imaging. One day after initiation of oral antibiotic and non-steroidal anti-inflammatory therapy, he developed worsening of the orbital inflammation and partial ophthalmoplegia. Oral steroids were commenced resulting in rapid resolution of symptoms within a few days and clinical stability at 2 months.The patient did not have any systemic features of COVID-19 but he was in close contact with his mother and with his partner who both had respiratory symptoms and tested positive for SARS-CoV-2 antigen (PCR testing) 4 weeks prior. PCR testing from nasopharyngeal swab was negative for SARS-CoV-2 RNA; however, the serological test was positive for IgM/IgG SARS-CoV-2 antibodies. Extensive laboratory workup including infectious and autoimmune screening and chest x-ray were unremarkable.Orbital inflammatory disease due to infectious process or immunological response may potentially occur in COVID-19 patients, although the causal relationship remains uncertain.

Influence of prior treatment protocol on intravitreal dexamethasone implant behavior in patients with diabetic macular edema in real-world practice.

BACKGROUND AND OBJECTIVE: Intravitreal dexamethasone implant (DEXI) has been placed as an effective option to treat diabetic macular edema (DME). However, there is no consensus on the best time to introduce it. We conducted a study to evaluate anatomical and functional behavior after the first DEXI according to previous treatment. RESEARCH DESIGN AND METHODS: This retrospective, real-world study between 2013 and 2020 investigated changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT at months 2 and 6 after the first DEXI in DME. Patients were divided into naive, early switch (≤3 anti-VEGF injections), or late switch (>3 anti-VEGF injections) groups. RESULTS: Among 112 consecutive eyes, mean BCVA and CMT improved significantly in all groups at month 2, with no difference between them. However, this improvement was not maintained at 6 months. The Naíve group presented better BCVA all over the study period. The previously treated groups, which started with worse initial visual acuity, showed more visual gain without reaching the BCVA of the naive group. CMT performance was similar between groups. CONCLUSIONS: There was similar anatomical and functional behavior in all groups. Poorer visual acuity at baseline was associated with worse functional outcome despite good anatomic response.

CYP1B1 mutations in Spanish patients with primary congenital glaucoma: phenotypic and functional variability.

PURPOSE: To analyze the contributions of cytochrome P4501B1 (CYP1B1) mutations to primary congenital glaucoma (PCG) in Spanish patients. METHODS: We analyzed, by polymerase chain reaction (PCR) DNA sequencing, the presence of promoter (-1 to -867) and exon CYP1B1 mutations in 38 unrelated Spanish probands affected by PCG. Functional analysis of nine identified mutations was performed measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected human embryonic kidney 293T (HEK-293-T) cells. RESULTS: We found a total of 16 different mutations in 13 (34.2%) index cases. The identified mutations included nine missense and three nonsense nucleotide changes, three small deletions, and a short duplication. Eleven probands were compound heterozygotes and two were heterozygotes. Six of the identified mutations were novel (A106D, E173X, F261L, E262X, W341X, and P513_K514del). Mutations T404fsX30 and R355fsX69 were the most prevalent among index cases and were detected in six (23.0%) and three (11.5%) patients, respectively. Functional analysis showed that the three nonsense mutants assayed (E173X, E262X, and W341X) and F261L were null alleles. Of the remaining mutants, four (P52L, G61E, Y81N, and E229K) showed catalytic activities ranging from 20% to 40% of wild-type CYP1B1 and high protein instability. Mutation P400S showed normal catalytic activity and moderate instability. These five mutants were classified as hypomorphic alleles. Patients carrying two null alleles showed severe phenotypes featured by very early PCG onset usually at birth or in the first month of life (0.6+/-0.9 months). Incomplete penetrance was detected in patients carrying hypomorphic alleles. CONCLUSIONS: Our data indicate that approximately one-third of Spanish patients with PCG carry loss-of-function CYP1B1 and show that null alleles are associated with the most severe phenotypes. Hypomorphic alleles may contribute to some cases of incomplete penetrance.

R124C and R555W TGFBI mutations in Spanish families with autosomal-dominant corneal dystrophies.

PURPOSE: Mutations in the transforming growth factor beta I (TGFBI) gene cause several types of autosomal-dominant corneal dystrophies. We investigated the role of this gene in two Spanish families affected by lattice type I or granular type I corneal dystrophies. METHODS: We recruited 13 subjects from two unrelated families diagnosed with autosomal dominant lattice type I or granular type I corneal dystrophies. Corneal phenotypes were assessed by slit lamp examination. Genomic DNA was obtained from blood samples, and exons 4, 11, 12, and 14, which contained mutation hot spots of the TGFBI gene, were screened for mutations by PCR DNA sequencing. RESULTS: We identified two TGFBI mutations: R124C (exon 4), which segregated with lattice type I corneal dystrophy, and R555W (exon 12), which segregated granular type I corneal dystrophy. Two single-nucleotide polymorphisms were also found, of which H428H was novel and F540F was previously reported. CONCLUSIONS: This is the first report of mutations in the TGFBI gene in Spanish families affected by corneal dystrophy. R124C and R555W TGFBI mutations cause lattice and granular type I corneal dystrophies in the studied families. Our results indicate that the genetic defects underlying corneal dystrophies in Spanish patients are similar to those found in other populations.

Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma.

PURPOSE: To investigate CYP1B1 gene mutations in Spanish patients with ocular hypertension (OHT) or primary open angle glaucoma (POAG). METHODS: The two coding exons of CYP1B1 were screened for sequence alterations by direct PCR DNA sequencing in 37 and 82 unrelated Spanish subjects diagnosed with OHT and POAG, respectively. As a control we used a group of 93 subjects from whom OHT or glaucoma were ruled out. RESULTS: We found three different predicted amino acid substitutions (Ala189Pro, Ala330Ser, and Ala443Gly) in three (8.1%) OHT subjects, and seven different mutations (Ser28Trp, Gly61Glu, Tyr81Asn, Gln144His, Arg145Trp, Glu229Lys, and Val409Phe) in nine (10.9%) glaucoma patients. These sequence variations showed higher frequencies in cases than in controls (as recently reported in French patients). They are predicted to produce a significant change in the amino acid sequence and affect conserved regions of the protein. All these missense mutations were found as heterozygots. In addition, four of them have been previously found in PCG and/or POAG patients, whereas the other six mutations (Ser28Trp, Gln144His, Arg145Trp, Ala189Pro, Ala330Ser, and Val409Phe) have not been previously described. Clinically, these mutations are associated with an age at diagnosis ranging from 12 to 58 years (mean 34.3 years) and from 48 to 77 years (mean 59.9 years) among OHT and glaucoma patients, respectively. CONCLUSIONS: Heterozygous CYP1B1 mutations could confer increased susceptibility to the development of POAG in the Spanish population.

WDR36 and P53 gene variants and susceptibility to primary open-angle glaucoma: analysis of gene-gene interactions.

PURPOSE: To investigate the role of WDR36 and P53 sequence variations in POAG susceptibility. METHODS: The authors performed a case-control genetic association study in 268 unrelated Spanish patients (POAG1) and 380 control subjects matched for sex, age, and ethnicity. WDR36 sequence variations were screened by either direct DNA sequencing or denaturing high-performance liquid chromatography. P53 polymorphisms p.R72P and c.97-147ins16bp were analyzed by single-nucleotide polymorphism (SNP) genotyping and PCR, respectively. Positive SNP and haplotype associations were reanalyzed in a second sample of 211 patients and in combined cases (n = 479). RESULTS: The authors identified almost 50 WDR36 sequence variations, of which approximately two-thirds were rare and one-third were polymorphisms. Approximately half the variants were novel. Eight patients (2.9%) carried rare mutations that were not identified in the control group (P = 0.001). Six Tag SNPs were expected to be structured in three common haplotypes. Haplotype H2 was consistently associated with the disease (P = 0.0024 in combined cases). According to a dominant model, genotypes containing allele P of the P53 p.R72P SNP slightly increased glaucoma risk. Glaucoma susceptibility associated with different WDR36 genotypes also increased significantly in combination with the P53 RP risk genotype, indicating the existence of a genetic interaction. For instance, the OR of the H2 diplotype estimated for POAG1 and combined cases rose approximately 1.6 times in the two-locus genotype H2/RP. CONCLUSIONS: Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in POAG susceptibility, although this finding must be confirmed in other populations.