Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.

Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.

Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.

Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.

Purpose: To describe the clinical presentation, ocular complications, treatment, and visual outcomes in a series of 17 patients from New Zealand with neuroretinitis secondary to Bartonella henselae. Methods: Retrospective cross-sectional single-center study from 2001 to 2024. Data was extracted from a clinical database of all patients treated for B. henselae over the past 23 years. Statistical analysis was performed using IBM SPSS Statistics ver. 26.0. Results: Seventeen patients (19 eyes) were included with 11 (65%) being female. The mean age at presentation was 28.3 ± 12.3 years (range, 13–60 years). The mean presenting visual acuity (Early Treatment Diabetic Retinopathy Study testing) was 50 ± 23 (range, 4–90). The mean final visual acuity was 78 ± 12 (range, 45–90). Eleven patients (65%) had cats or kittens at home, with only one (6%) recounting a history of being scratched. Eight patients (47%) demonstrated the characteristic macular star at presentation, with all eventually developing macular star within a mean of 6 days. Four patients (24%) had macular oedema, three (18%) had vasculitis, two (12%) had uveitis, two (12%) had disc granuloma, and one (6%) had multifocal chorioretinitis. Six patients (35%) were treated with rifampicin and doxycycline, one (6%) with rifampicin and azithromycin, two (12%) with doxycycline only, two (12%) with co-trimoxazole monotherapy, and one patient (6%), who was breast-feeding, was treated with erythromycin. Four patients (24%) did not have receive any treatment. Conclusions The characteristic macular star is not always manifest at initial presentation for patients with neuroretinitis secondary to B. henselae, nor is there always a preceding history of cat exposure. Not all patients require treatment to have a good visual outcome, and the immune status of the patient is important.

Multiple morphological abnormalities of the flagella (MMAF) represent a severe form of sperm defects leading to asthenozoospermia and male infertility. In this study, we identified a novel homozygous splicing mutation (c.871-4 ACA>A) in the adenylate kinase 7 (AK7) gene by whole-exome sequencing in infertile individuals. Spermatozoa from affected individuals exhibited typical MMAF characteristics, including coiled, bent, short, absent, and irregular flagella. Transmission electron microscopy analysis showed disorganized axonemal structure and abnormal mitochondrial sheets in sperm flagella. Immunofluorescence staining confirmed the absence of AK7 protein from the patients' spermatozoa, validating the pathogenic nature of the mutation. This study provides direct evidence linking the AK7 gene to MMAF-associated asthenozoospermia in humans, expanding the mutational spectrum of AK7 and enhancing our understanding of the genetic basis of male infertility.
Humans ; Male ; Sperm Tail/ultrastructure* ; Homozygote ; Consanguinity ; Asthenozoospermia/pathology* ; Infertility, Male/genetics* ; Mutation ; Pakistan ; Adenylate Kinase/genetics* ; Adult ; Pedigree ; RNA Splicing ; Exome Sequencing ; Spermatozoa

Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella (MMAF). Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement. Mammalian sperm-associated antigen 17 ( SPAG17 ) encodes a conserved axonemal protein of cilia and flagella, forming part of the C1a projection of the central apparatus, with functions related to ciliary/flagellar motility, skeletal growth, and male fertility. This study investigated two novel homozygous SPAG17 mutations (M1: NM_206996.2, c.829+1G>T, p.Asp212_Glu276del; and M2: c.2120del, p.Leu707*) identified in four infertile patients from two consanguineous Pakistani families. These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa. Quantitative real-time polymerase chain reaction (PCR) of patients' spermatozoa also revealed a significant decrease in SPAG17 mRNA expression, and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella. However, no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients. Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls. Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17 (SPATA17), a component of the C1a projection, and sperm-associated antigen 6 (SPAG6), a marker of the spring layer, revealed disrupted expression of both proteins in the patients' spermatozoa. Altogether, these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme, expanding the phenotypic spectrum of SPAG17 mutations in humans.
Humans ; Male ; Infertility, Male/pathology* ; Sperm Tail/ultrastructure* ; Homozygote ; Microtubule-Associated Proteins/genetics* ; Axoneme/genetics* ; Spermatozoa/ultrastructure* ; Adult ; Mutation ; Sperm Motility/genetics* ; Pedigree ; Microtubules ; Microtubule Proteins/genetics*

Multiple morphological abnormalities of sperm flagella (MMAF) is a severe form of asthenoteratozoospermia, characterized by morphological abnormalities and reduced motility of sperm, causing male infertility. Although approximately 60% of MMAF cases can be explained genetically, the etiology of the remaining cases is unclear. Here, we identified two novel compound heterozygous variants in the gene, dynein axonemal heavy chain 10 ( DNAH10 ), in three patients from two unrelated Pakistani families using whole-exome sequencing (WES), including one compound heterozygous mutation ( DNAH10 : c.9409C>A [p.P3137T]; c.12946G>C [p.D4316H]) in family 1 and another compound heterozygous mutation ( DNAH10 : c.8849G>A [p.G2950D]; c.11509C>T [p.R3687W]) in family 2. All the identified variants are absent or rare in public genome databases and are predicted to have deleterious effects according to multiple bioinformatic tools. Sanger sequencing revealed that these variants follow an autosomal recessive mode of inheritance. Hematoxylin and eosin (H&E) staining revealed MMAF, including sperm head abnormalities, in the patients. In addition, immunofluorescence staining revealed loss of DNAH10 protein signals along sperm flagella. These findings broaden the spectrum of DNAH10 variants and expand understanding of the genetic basis of male infertility associated with the MMAF phenotype.
Adult ; Humans ; Male ; Alleles ; Asthenozoospermia/pathology* ; Axonemal Dyneins/genetics* ; Dyneins/genetics* ; Exome Sequencing ; Infertility, Male/pathology* ; Mutation ; Pakistan ; Pedigree ; Sperm Tail/pathology*

The syndrome of multiple morphological abnormalities of the sperm flagella (MMAF) is one of the most serious kinds of sperm defects, leading to asthenoteratozoospermia and male infertility. In this study, we use whole-exome sequencing to identify genetic factors that account for male infertility in a patient born from a consanguineous Pakistani couple. A homozygous frameshift mutation (c.1399_1402del; p.Gln468ArgfsTer2) in axonemal dynein light chain domain containing 1 ( AXDND1 ) was identified in the patient. Sanger sequencing data showed that the mutation was cosegregated recessively with male infertility in this family. Papanicolaou staining and scanning electron microscopy analysis of the sperm revealed severely abnormal flagellar morphology in the patient. Immunofluorescence and western blot showed undetectable AXDND1 expression in the sperm of the patient. Transmission electron microscopy analysis showed disorganized sperm axonemal structure in the patient, particularly missing the central pair of microtubules. Immunofluorescence staining showed the absence of sperm-associated antigen 6 (SPAG6) and dynein axonemal light intermediate chain 1 (DNALI1) signals in the sperm flagella of the patient. These findings indicate that AXDND1 is essential for the organization of flagellar axoneme and provide direct evidence that AXDND1 is a MMAF gene in humans, thus expanding the phenotypic spectrum of AXDND1 frameshift mutations.
Humans ; Male ; Sperm Tail/ultrastructure* ; Frameshift Mutation ; Infertility, Male/pathology* ; Pakistan ; Pedigree ; Consanguinity ; Axonemal Dyneins/genetics* ; Adult ; Spermatozoa ; Exome Sequencing

In the context of ARVC, a systematic review of the validation of the ARVC risk score can provide insights into the accuracy and reliability of this score in identifying patients at high risk of ARVC. Digital databases were searched to identify the relevant studies using Medical Subject Headings (MeSH). A total of 8 studies were included in this systematic review. A total of 8 studies were included in this review. The review found that the sensitivity of the ARVC risk scores ranged from 80 to 95%, and the specificity ranged from 31 to 79%. The PPV was 55%, and the NPV was 88%. The ARVC score provided a C-index for a 5-year VA risk prediction of 0.84 [95% CI (0.74–0.93)] and a Harrell C-index of 0.70 (95% CI 0.65–0.75). The calibration slope was 1.01 (95% CI 0.99–1.03). ARVC score demonstrated a significant event 5-year threshold between 15 and 20% and the classical ARVC 5-years/freedom-from-VA rate was 0.76(0.66–0.89) and the non-classical form 5-years/freedom-from-VA rate was 0.58 (0.43–0.78). In conclusion, the validation of ARVC risk scores is an essential step toward improving the accuracy of ARVC diagnosis and risk stratification. Further studies are needed to establish the accuracy and reliability of ARVC risk scores and to address the limitations of the current evidence.