Research progress of microglia activation in the regulatory mechanism of ret-initis pigmentosa / 眼科新进展

Retinitis pigmentosa(RP)is a hereditary retinal degenerative ocular disease.Accumulating studies have demonstrated that microglia(MG)activation occurs at the early stage of retinal degeneration.MG,as immune cells in the central nervous system and retina,are involved in the formation of the front line of the innate immune system,exhibiting neuroprotective or neurotoxic effects in various neurodegenerative processes.The neurotoxic or neuroprotective effects re-sulting from microglia activation may influence the pathological progression of RP.Consequently,therapeutic strategies tar-geting MG,aiming to modulate disease progression and outcome by balancing neuroprotective or neurotoxic effects,repre-sent a promising avenue for future treatment.

The 504th case: Multiple lymph node enlargement, renal insufficiency, blindness, and white matter lesions of the brain / 中华内科杂志

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.

Correlation of clinical manifestations of retinitis pigmentosa complicated with cataract and neutrophil-to-lymphocyte ratio / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the neutrophil-to-lymphocyte ratio(NLR)in patients with retinitis pigmentosa(RP)complicated with cataract, and to explore its correlation with the clinical characteristics of RP patients complicated with cataract.METHODS: The retrospective study included 79 RP patients(125 eyes)complicated with cataract who received cataract surgery at our hospital from January 2008 to December 2018, among which 63 cases(63 eyes)were finally enrolled in the RP complicated with cataract group after the exclusion of patients with early age of onset. Another 63 age- and sex-matched patients(63 eyes)with age-related cataract(ARC)who had cataract surgery during the same period in our hospital were enrolled in the ARC group. The clinical data and NLR were collected, and the correlation of clinical manifestations with NLR in RP patients complicated with cataract was analyzed.RESULTS: The NLR in RP patients complicated with cataract was significantly higher than that in the ARC group [1.79(1.32, 2.27)vs 1.58(1.32, 1.98), P=0.032]. NLR was associated with the severity of posterior subcapsular cataract(PSC), zonular deficiency, and preoperative best-corrected visual acuity(>1 LogMAR). Receiver operating curve showed that NLR ≥1.36 could predict higher degrees(>P1)of RP complicated PSC(AUC=0.803, 95%CI 0.672-0.934, P=0.002), NLR ≥2.12 could predict zonular weakness in RP patients complicated with cataract(AUC=0.796, 95%CI 0.665-0.928, P=0.002), while NLR ≥1.51 could predict RP patients with worse preoperative BCVA(AUC=0.667, 95%CI 0.540-0.793, P=0.015).CONCLUSION: NLR in RP patients complicated with cataract is significantly higher than that in ARC patients, and it is correlated with the clinical manifestations of RP patients with cataract. NLR can be used as a potential predictor to evaluate the severity of clinical manifestations of RP complicated with cataract.

Photobiomodulation therapy as a new hope therapy for retinitis pigmentosa: a systematic review / Terapia de fotobiomodulação como nova terapia de esperança para retinite pigmentosa: uma revisão sistemática

ABSTRACT Retinitis pigmentosa is one of the leading causes of hereditary blindness in developed countries and unfortunately there is currently no cure. Photobiomodulation therapy can penetrate the retina and optic nerve and restore the function of damaged mitochondria as an intracellular target. This study is proposed to review and analyze photobiomodulation as a strategy that has the potential to be a new hope therapy and non-invasive treatment for retinitis pigmentosa in the long term. PubMed® and Google Scholar were used to perform a systematic review of photobiomodulation as a therapy for retinitis pigmentosa. Using PRISMA 2020 Guidelines, we include seven studies in this review. The inclusion criteria for each study were as follows: the study documented the use of photobiomodulation therapy for retinitis pigmentosa, was conducted in human eyes or animals' eye, its full text was in English, and it published in the last 10 years. We anticipated that most studies would be experimental design, we evaluated the quality of eligible studies using relevant items from the ROBINS-I, which is the recommended tool to evaluate experimental study. There is a clinical improvement in visual acuity and visual fields. Further eye examination showed functional and outer nuclear layer preservation, decline waveforms of electroretinogram slower than control, disruption of retinal pigment epithelium, and preserved photoreceptor nuclei twice thicker than control (p < 0.05). Photobiomodulation also increases retinal mitochondrial function and maintains mitochondrial redox state, revealing significant recovery of photoreceptors' cell function. Photobiomodulation showed significant change in clinical improvement, mitochondrial repair, and retinal layer thickening; thus, photobiomodulation can be a new hope for therapeutic strategies for retinitis pigmentosa. Several studies only have a few participants, so it does not provide a long-term outcome in retinitis pigmentosa.

RESUMO A retinite pigmentosa é uma das principais causas de cegueira hereditária em países desenvolvidos e, infelizmente, não há cura atualmente. A terapia de fotobiomodulação pode penetrar na retina e no nervo óptico e restaurar a função das mitocôndrias danificadas como alvo intracelular. Este estudo propõe-se a rever e a analisar a fotobiomodulação como estratégia que tem potencial para ser uma nova esperança terapêutica e tratamento não invasivo para a retinite pigmentosa a longo prazo. PubMed® e Google Scholar foram usados para realizar uma revisão sistemática da fotobiomodulação como terapia para retinite pigmentosa. Usando as diretrizes PRISMA de 2020, incluímos sete estudos nesta revisão. Os critérios de inclusão para cada estudo foram os seguintes: que tivesse documentado o uso de terapia de fotobiomodulação para retinite pigmentosa; o procedimento tivesse sido realizado em olhos humanos ou olhos de animais, e o texto fosse completo, em inglês, e publicado no último 10 anos. Previmos que a maioria dos estudos seria de desenho experimental, avaliamos a qualidade dos estudos elegíveis usando itens relevantes do ROBINS-I, que é a ferramenta recomendada para avaliação de estudo experimental. Houve melhora clínica da acuidade visual e dos campos visuais. O exame oftalmológico adicional mostrou preservação funcional e da camada nuclear externa; declínio das formas de onda do eletrorretinograma mais lento que o controle; ruptura do epitélio pigmentar da retina e núcleos fotorreceptores preservados duas vezes mais espessos que o controle (p < 0,05). A fotobiomodulação também aumenta a função mitocondrial da retina e mantém o estado redox mitocondrial, revelando uma recuperação significativa da função celular dos fotorreceptores. A fotobiomodulação mostrou mudança significativa na melhora clínica, reparo mitocondrial e espessamento da camada retiniana. Assim, a fotobiomodulação pode ser uma nova esperança para estratégias terapêuticas para retinite pigmentosa. Vários estudos têm apenas alguns participantes e, por isso, não fornecem um resultado a longo prazo na retinite pigmentosa.

Síndrome de Bardet-Biedl: A propósito de un caso / Bardet-Biedl syndrome: About a case

El síndrome de Bardet-Biedl (SBB) es una entidad poco frecuente, con gran heterogeneidad clínica y genética. Pertenece a las ciliopatías y tiene un modo de herencia autosómico recesivo. Hasta la fecha se han identificado más de 26 genes asociados. Afecta múltiples sistemas con compromiso oftalmológico, renal, cognitivo, esquelético, gonadal y ponderal. Su diagnóstico se basa en criterios clínicos y se confirma mediante estudios genéticos específicos. Presentamos el caso de un paciente de 2 años y 7 meses de edad, con polidactilia, obesidad, retraso del neurodesarrollo y afección renal en quien se arribó al diagnóstico clínico de SBB con posterior confirmación mediante estudio molecular. Se detectó una variante patogénica en homocigosis en el gen BBS2. La sospecha y confirmación diagnóstica permitieron el manejo adecuado del paciente, planificar el seguimiento apropiado y completar el asesoramiento genético familiar

Bardet-Biedl syndrome (BBS) is a rare entity that holds a great clinical and genetic heterogeneity. It is a ciliopathy and has an autosomal recessive inheritance. To this day more than 26 associated genes have been identified. It affects multiple aspects predominantly ophthalmological, renal, cognitive, skeletal, gonadal and weight. The diagnosis is based on clinical criteria and confirmed by specific genetic studies. We describe a case of a 2-year-and 7 month old patient with polydactyly, obe39 sity, neurodevelopmental delay and kidney dysplasia in which clinical diagnosis was suspected by criteria and subsequently has confirmation by molecular study. An homozygous pathogenic variant was detected in the BBS2 gene. The diagnostic suspicion and later confirmation allowed the proper management of this patient as well as an appropriate follow-up and complete genetic family counseling

Epidemic retinitis during pregnancy

Purpose: To study the clinical presentation and treatment outcome of epidemic retinitis (ER) during pregnancy. Methods: This is a retrospective, observational chart review of pregnant patients diagnosed with ER from January 2014 to February 2023. Demographic details, month of pregnancy at the onset of ocular symptoms, history of present illness, clinical manifestations, and treatment outcomes were studied. Results: In 9 years, ER was seen in 86 females, of whom 12 (13.9%) were pregnant. Twenty?one eyes of those 12 patients were studied. Most of the patients presented in the sixth month of pregnancy (range: 5–9 months, mean: 6.3 months). Physicians diagnosed viral exanthematous fever in six, typhoid in three, and suspected rickettsia in one patient. Medical termination of pregnancy (MTP) was performed in two patients before presentation. Weil–Felix test was positive in five, Brucella in one, WIDAL in three, and coronavirus disease 2019 (COVID?19) IgG and dengue IgG in one patient each. Oral antibiotics were given in five patients (two post?medical termination of pregnancy [MTP]) for the retinitis. All except four received oral steroids. Mean presenting corrected distant visual acuity (n = 21) was 20/125 (range: 20/20–20/20,000), which improved to (n = 18) 20/30 (range: 20/20–20/240). Macular edema (n = 11) resolved in 33.18 days (range: 20–50 days), and retinitis (n = 13) resolved in 58 days (range: 30–110 days). Ocular and systemic examination of newborn was possible in two and the babies were normal. Conclusion: ER is seen commonly at the beginning of the third trimester. Lack of antibiotics may delay the resolution of retinitis. Ocular health needs to be assessed in larger series to conclude absence of retinal involvement in newborns.

Epidemic retinitis during the COVID-19 pandemic

Purpose: To study the impact of the novel coronavirus disease?2019 (COVID?19) pandemic on incidence, seasonal variation, clinical presentation, and disease outcome of epidemic retinitis (ER) and to compare clinical outcomes with positive and negative COVID?19 serology. Methods: This is a retrospective, observational study conducted at a tertiary eye care hospital from August 2020 to June 2022. A graph of ER cases against the month of presentation was compared with the graph of the COVID?19 pandemic in the same region. Cases presented before COVID?19 vaccination, with positive COVID?19 serology (Group 1) were compared with cases with negative serology (Group 2). Results: One hundred and thirty?two cases of ER were seen. The least number of cases were seen during and immediately after the peak of the pandemic (May 2021–August 2021). COVID?19 serology was positive in 13 (22 eyes)/60 (21.6%) unvaccinated cases. Along with COVID?19, positive serology for other ER etiologies was seen in 5/13 cases (38.4%). All patients received oral doxycycline with/without steroids. Groups 1 and 2 included 22 and 21 eyes of 13 cases each. Macular edema resolved in 43.6 and 32 days in groups 1 and 2, respectively. Retinitis resolved at 1 month in both groups. Corrected distant visual acuity was 20/50 and 20/70 at the presentation, which improved to 20/20 and 20/25 in groups 1 and 2, respectively. Mean and median follow?up was 6 months and 4.5 months, respectively, in both groups. No complications or recurrences were seen. Conclusion: No significant impact of the COVID?19 pandemic on ER was observed

Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel?based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single?center study of 107 RP patients who had undergone next?generation sequencing?based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype–phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel?based testing for IRD genes followed by co?segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5–55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0–3.0). At presentation, over one?third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well?defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump?like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS?based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene?based therapies.

Phenotypic heterogeneity in family members of patients with retinitis pigmentosa

Purpose: To describe the phenotypic variations in family members of patients with retinitis pigmentosa (RP) with different modes of inheritance and to assess the ocular abnormalities in RP families. Methods: A descriptive analysis of three types of inheritance of RP was carried out, where 64 family members were examined at a tertiary eye care center, South India. They underwent comprehensive eye examination, fundus photography, fundus autofluorescence (FAF), full?field electroretinogram (FFERG), and spectral domain optical coherence tomography (SD?OCT). Analysis was performed between mild and severe forms of abnormalities to delineate retinal structural and functional defects in RP families. Results: The mean age was 38.55 ± 17.95 years. Males were 48.4%. In autosomal recessive and X?linked recessive groups, 74.2% and 77.3%, respectively, were asymptomatic, whereas in autosomal dominant group, 27.3% were asymptomatic. The proportion of the cases with abnormalities in all three groups was higher on ERG (59.6%), followed by OCT (57.5%), visual acuity (43.7%), peripheral FAF (23.5%), and macular FAF (11.8%). However, these abnormalities and the clinical pictures of the family members had no statistical difference across the three groups of inheritance. Conclusion: Structural and functional retinal alterations were noted in four out of five asymptomatic members, suggesting the need for careful screening of RP families and the pressing need for pre?test (genetic) counseling

Challenges of managing HIV cytomegalovirus co-infection in the presence of pancytopenia

A 60-year-old male patient who presented with generalized weakness and low-grade fever was diagnosed to be human immunodeficiency virus (HIV) positive with a CD4 count of 17. Routine laboratory investigations revealed pancytopenia. Serum cytomegalovirus (CMV) DNA polymerase chain reaction (PCR) was positive and fundoscopy showed CMV retinitis in the right eye. The patient was started on tablet valganciclovir. After 2 weeks, the patient was brought back in an altered sensorium. He was found to have hyponatremia which was corrected. He was started on antiretroviral therapy and tablet valganciclovir was continued. The patient came back again after one and a half months with a urinary tract infection and fissure-in-ano. He was found to have severe neutropenia. Valganciclovir was stopped. He was started on injection granulocyte colony-stimulating factor. The patient clinically improved and his hematological parameters became normal. Patients having HIV and CMV co-infection with pre-existing pancytopenia have to be closely monitored as the medicines used for treatment can exacerbate the existing conditions.

Demographic and Clinical Profile of Patients with Low Vision: A Hospital Based Study

Background: Vision impairment is a significant problem in our country. The purpose of this study was to evaluate the causes and to record the demographic profile of patients with low vision. Material & Methods: After taking permission from ethical committee, the study was conducted on 250 patients presenting in low vision clinic of Regional Institute of Ophthalmology punjab in north India .A detailed examination and information regarding the demographic and clinical characteristics of the patients were recorded .the visual acuity of all the patients were determined using Snellen chart followed by anterior and posterior segment examination using a slit-lamp bio microscope and direct and /or indirect ophthalmoscope.Refraction was done in all the subjects and Best corrected visual acuity was recorded. Their demographic and clinical profile were analyzed using SPSS software. Results: Majority of the patients presenting with low vision were found to be above 56 years of age with higher prevalence in rural (54.40%) than in urban (45.60%) population. Male (65.60%)were predominant than females(34.40%) .Major etiological causes were Diabetic retinopathy 76 (30 .40%) followed by Pathological Myopia (21.20%), ARMD (14.80%), Retinitis pigmentosa (6.80%) and Glaucoma (6.00%). Conclusion: Diabetic retinopathy and pathological myopia were the predominant causes of low vision. Patients from rural background were more affected than urban areas.

Enfermedades crónicas no transmisibles en pacientes y familias con retinosis pigmentaria

Fundamento: la retinosis pigmentaria, enfermedad ocular de origen genético y baja prevalencia, progresa lentamente en años hacia el deterioro visual severo y afecta el desempeño social. En el Servicio de Oftalmología del Hospital Docente Clínico Quirúrgico Dr. Salvador Allende, existe un protocolo asistencial institucional que incluye la atención sistemática e integral de los afectados. Objetivo: identificar las enfermedades crónicas no transmisibles en pacientes con retinosis pigmentaria y en sus familiares. Métodos: estudio descriptivo, prospectivo, realizado entre marzo 2016-marzo 2022, con muestreo no probabilístico e intencionado. Se seleccionaron pacientes y familias registradas en la base de datos del servicio, residentes en los municipios Cerro y Plaza, en La Habana. Resultados: de 145 personas estudiadas (74 enfermos de retinosis pigmentaria y 71 familiares), 138 (95,1 %) presentaban enfermedades crónicas no transmisibles, entre las que se destacan la hipertensión arterial (29,7 %), la diabetes mellitus (21,0 %) y la asociación de ambas (13,0 %). En la dispensarización comunitaria se incluyen en el Grupo 4 las personas con déficit visual y además en otros grupos de dispensarización para atender mejor los factores de riesgo y enfermedades crónicas no transmisibles halladas en ellos. Conclusiones: la identificación de las enfermedades crónicas no transmisibles fue útil, para desplegar una atención médica holística e interdisciplinaria que facilite la prevención de enfermedades y complicaciones, permita preservar la visión, optimizar la rehabilitación visual y la calidad de vida. Se recomienda aplicar atento cuidado y mejorar la educación sanitaria en pacientes con retinosis pigmentaria.

Background: retinitis pigmentosa, an ocular disease of genetic origin and low prevalence, slowly progresses over years towards severe visual impairment and affects social performance. In the Ophthalmology Service of the Dr. Salvador Allende Clinical Surgical Teaching Hospital, there is an institutional care protocol that includes systematic and comprehensive care for those affected. Objective: to identify chronic non-communicable diseases in patients with retinitis pigmentosa and their relatives. Methods: descriptive, prospective study carried out between March 2016-March 2022, with non-probabilistic and intentional sampling. Patients and families registered in the service's database, residing in the Cerro and Plaza municipalities, in Havana, were selected. Results: of 145 people studied (74 patients with retinitis pigmentosa and 71 relatives), 138 (95.1%) had non-communicable chronic diseases, among which arterial hypertension (29.7%), diabetes mellitus (21 0.0%) and the association of both (13.0%). In community dispensing, people with visual impairment are included in Group 4 and also in other dispensing groups to better attend to the risk factors and chronic non-communicable diseases found in them. Conclusions: the identification of chronic non-communicable diseases was useful to deploy holistic and interdisciplinary medical care that facilitates the prevention of diseases and complications, preserves vision, optimizes visual rehabilitation and quality of life. It is recommended to apply attentive care and improve health education in patients with retinitis pigmentosa.

Visual impairment and blindness due to retinitis pigmentosa in India: 15-year follow-up of the Andhra Pradesh Eye Disease Study cohort

Purpose: To assess the incidence, visual impairment, and blindness due to retinitis pigmentosa (RP) in a rural southern Indian cohort. Methods: This is a population?based longitudinal cohort study of participants with RP from the Andhra Pradesh Eye Disease Study (APEDS) cohorts I and III, respectively. The study included participants with RP of APEDS I who were followed until APEDS III. Their demographic data along with ocular features, fundus photographs, and visual fields (Humphrey) were collected. Descriptive statistics using mean ± standard deviation with interquartile range (IQR) were calculated. The main outcome measures were RP incidence, visual impairment, and blindness as per the World Health Organization (WHO) definitions. Results: At baseline (APEDS I), 7771 participants residing in three rural areas were examined. There were nine participants with RP with a mean age at baseline of 47.33 ± 10.89 years (IQR: 39–55). There was a male preponderance (6:3), and the mean best?corrected visual acuity (BCVA) of 18 eyes from nine participants with RP was 1.2 ± 0.72 logarithm of minimum angle of resolution (logMAR; IQR: 0.7–1.6). Over a mean follow?up duration of 15 years, 5395/7771 (69.4%) were re?examined, which included seven RP participants from APEDS 1. Additionally, two new participants with RP were identified; so, the overall incidence was 370/ million in 15 years (24.7/million per year). The mean BCVA of 14 eyes of seven participants with RP who were re?examined in APEDS III was 2.17 ± 0.56 logMAR (IQR: 1.8–2.6), and five of these seven participants with RP developed incident blindness during the follow?up period. Conclusion: RP is a prevalent disease in southern India that warrants appropriate strategies to prevent this condition.

Early occurrence of primary angle-closure glaucoma in a patient with retinitis pigmentosa and CRB1 gene variations / Manifestação precoce de glaucoma de ângulo fechado em paciente com retinopatia por mutação no gene CRB1

ABSTRACT We describe the case of a 15-year-old girl with decreased visual acuity associated with elevated intraocular pressure in both eyes and angle closure on gonioscopy. She also presented attenuation of retinal vessels and optic disc pallor with large excavation in the left eye. Ultrasound biomicroscopy revealed an anteriorly positioned ciliary body and absence of ciliary sulcus, confirming the plateau iris configuration. Spectral-domain optical coherence tomography revealed a bilateral cystoid macular edema. Genetic screening revealed heterozygous variants of the Crumbs homolog 1 (CRB1) gene (c.2843G>A and c.2506C>A). The patient underwent trabeculectomy for intraocular pressure control and topical treatment for macular edema. This case highlights the importance of performing gonioscopy and evaluating intraocular pressure in patients with a shallow anterior chamber despite young age. In addition, it also shows the importance of genetic screening, when available, in elucidating the diagnosis and providing patients and their families' information on the patient's prognosis and possible therapeutic options.

RESUMO Nós descrevemos um caso de uma paciente de 15 anos com queda de acuidade visual e aumento da pressão intraocular em ambos os olhos, juntamente com fechamento angular no exame de gonioscopia. Na fundoscopia a paciente apresentava atenuação dos vasos retinianos, palidez de disco e aumento de escavação em olho esquerdo. Ao exame da biomicroscopia ultrassônica, foi evidenciado corpo ciliar anteriorizado e ausência de sulco ciliar em ambos os olhos, relevando presença de íris em plateau. Ao exame de tomografia de coerência óptica, visualizamos presença de edema macular cistoide bilateral. O screening genético revelou heterozigose no gene CRB1 (c.2843G>A and c.2506C>A), confirmando o diagnóstico de retinose pigmentar. Este caso reforça a importância do exame de gonioscopia e da avaliação da pressão intraocular em pacientes em câmara rasa, mesmo em pacientes jovens. Além disso, mostra a importância do screening genético como ferramenta útil para elucidação diagnóstica.

Monitoring Weil–Felix test in epidemic retinitis

Purpose: The objective was to study the positivity of the Weil–Felix test (WFT) in epidemic retinitis (ER) during the course of the disease. Methods: This is a retrospective, observational case series of patients diagnosed with ER and presented to a tertiary eye care hospital in south India. Patients with positive WFT at the presentation, and who underwent a follow?up WFT during or after the resolution of ER were studied from September 2019 to March 2022. Patient’s demographics, timings of clinical presentation and resolution, and investigation details with a special focus on WFT positivity and its duration were noted. Results: Sixteen patients were studied. Patients presented after 5 weeks of the fever (range: 2?12 weeks, median: 4). After 1?2 months, WFT was still positive in eight patients (50%). Only in one patient titers increased after 1 month, while in others, the titers decreased (n = 11) or remained the same (n = 4). Repeated tests in those patients (n = 6) after 3?4 months turned negative. Resolution of ER was seen at 1.35 months (range: 1?3 months) after the presentation. The mean duration for WFT to turn negative was 2 months from the presentation (range: 1?4 months) or 3.2 months of the fever (range: 1.5?6 months). Conclusion: In contrast to the reported physician’s observation of increasing titers of WFT after rickettsial fever, ophthalmologists may observe decreasing WFT titers in ER. The clinical resolution of ER may precede the normalization of WFT. Follow?up WFT titers should be studied in larger series in confirmed cases of rickettsial?ER to validate the affordable and readily available WFT in India

Literature analysis of ocular adverse drug reactions related to dupilumab / 中国药房

OBJECTIVE To analyze the clinical manifestation and characteristics of ocular adverse drug reaction （ADR） related to dupilumab， so as to provide reference for clinically safe drug use. METHODS Retrieved from CNKI， Wanfang data， VIP and PubMed databases， the case reports about ocular ADR caused by dupilumab were collected， and then analyzed statistically in terms of gender， age， primary disease， drug use， occurrence time of ADR， main clinical manifestations， treatment or outcome， etc. RESULTS A total of 20 pieces of literature were selected， involving 46 patients， among which there were 29 males and 17 females. Mainly patients were under 60 years old. The results of the association evaluation was given as follows： 13 were “very likely” and 33 were “likely”. All patients were treated with dupilumab for atopic dermatitis （AD） without off-label medication. The occurrence time of ADR was 2 weeks to 2 years after administration， mainly within 6 months after medication. All patients received dupilumab monotherapy except that 3 patients with hypertension and 1 patient with chronic obstructive pulmonary disease and human immunodeficiency virus received other drugs simultaneously. Twenty-eight patients had a history of allergic disease， and 11 patients had a history of eye disease. Ocular ADRs were mainly conjunctivitis and uveitis， and the clinical manifestations mainly included conjunctival congestion， swelling， eye secretions， etc. Ten patients developed severe ADR， including uveitis， severe conjunctivitis， and tear point stenosis； 45 patients were improved after symptomatic treatment. AD， serious initial symptoms of AD， allergic disease and underlying ocular diseases might be the high-risk factors of ocular ADR caused by dupilumab. CONCLUSIONS Whether the patient has the history of allergic diseases and basic eye diseases should be asked in detail before clinical use of dupilumab. When using the drug， attention should be paid to monitoring whether the patient has intraocular inflammation， be alert to the occurrence of new or serious ADR， and give timely symptomatic treatment to ensure the safety of drug use.

VPS13B gene variation and clinical phenotype of Cohen syndrome in a Chinese Han family / 中华实验眼科杂志

Objective:To analyze the pathogenicity and clinical characteristics of patients with Cohen syndrome caused by a compound heterozygous variation of VPS13B gene. Methods:A pedigree investigation was conducted.A Chinese Han family with Cohen syndrome was recruited from Henan Eye Hospital in September 2021.There were three members of two generations in this family, including one patient.The clinical data of the proband and his parents were collected, and the relevant ophthalmic and general examinations were performed to evaluate the clinical phenotype.The peripheral venous blood samples of the family members were collected to extract whole genomic DNA, and the whole exome sequencing was performed.Sanger sequencing and pedigree co-segregation analysis were performed among the family members.According to the ACMG guidelines, the pathogenicity of the selected variants was evaluated and the online tools were used to predict the pathogenicity of the variants.Relevant literature of Cohen syndrome were retrieved in Online Mendelian Inheritance in Man (OMIM) and PubMed, China National Knowledge Infrastructure and Wanfang databases by taking Cohen syndrome and VPS13B gene as the searching keywords.The clinical manifestations and pathogenic variants of patients in the literature were summarized, and the relationship between genotype and clinical phenotype was analyzed.This study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[15]). Both the subject and the patient's guardian were aware of the study purpose and method.Written informed consent was obtained. Results:The family was consistent with autosomal recessive inheritance.The proband, a 5-year-old male, had bilateral night blindness with photophobia, ptosis, lower eyelid entropion, and trichiasis; high myopia in both eyes; osteoblastoid pigmentation in the peripheral retina, atrophy and thinning of the outer layer of the peripheral retina, extinguished flashing electroretinogram; global growth retardation, typical facial features, slender fingers and toes, flatfoot, foot valgus, dystonia, no cardiac abnormalities; excessively cheerful personality.The clinical manifestations of the proband were consistent with Cohen syndrome.No obvious abnormality was found in the clinical phenotype and the auxiliary examination of the proband's parents.Whole exon sequencing revealed that the proband carried two heterozygous variations, a nonsense variation c. 11713C>T(p.Gln3905*) and a splicing variation c. 6940+ 1G>T.Sanger sequencing confirmed that the above variations were co-segregated in this family.c.11713C>T(p.Gln3905*) was a novel variant, which prematurely terminated the protein encoded by it and affected the normal function of the protein.The two variations were pathogenic variants according to the ACMG guidelines.A total of 12 articles on variants and clinical characteristics of Cohen syndrome in China were retrieved.Combined with the results of this study, a total of 24 VPS13B variants were found in Chinese patients, of which the incidence of frameshift variation was 41.7%(10/24), missense variation 20.8%(5/24), splicing variation 20.8%(5/24) and nonsense variation 16.7%(4/24), respectively.The onset age of patients with Cohen syndrome was from 28 days to 12 years old.The symptoms such as nerve system, eye, brain, and bone were sporadic, and the clinical manifestations were highly heterogeneous. Conclusions:A novel pathogenic variation c. 11713C>T is found in the VPS13B gene of the Cohen syndrome pedigree in this study, and expands the pathogenic variation spectrum of the VPS13B gene.The clinical manifestations of Cohen syndrome are highly heterogeneous.

Advances in intravitreal ganciclovir treatment of cytomegalovirus retinitis after hematopoietic stem cell transplantation / 中华实验眼科杂志

Hematopoietic stem cell transplantation (HSCT) brings the possibility to prolong survival for patients with different types of hematological diseases, but patients may be complicated with cytomegalovirus retinitis (CMVR) due to immunocompromised state.Intravitreous injection of ganciclovir (IVG) is a major treatment in CMVR after HSCT, but there are significant differences in the dosage and frequency among existing IVG protocols due to lack of standardized consensus or guidelines.High-dose IVG therapy and a follow-up plan based on aqueous humor virus load and cytokine monitoring have been applied in clinical practice, and it has been reported to shorten treatment duration and reduce number of injections.Reports of retinal toxicity caused by IVG are rare, and more exploration is needed to determine the safe dose range of IVG.This article reviewed the advances in IVG treatment of CMVR after HSCT focusing on the acting mechanism of ganciclovir, the problems in systematic application, the treatment plan involving intravitreal injection, and the retinal toxicity of intravitreal injection.

Inhibition of photoreceptor apoptosis in mice with retinitis pigmentosa through NF-κB/NLRP3 pathway suppression with Lycium barbarum polysaccharide / 数字中医药（英文）

Objective@# To explore whether Lycium barbarum polysaccharide (LBP) can reduce the apoptosis of retinal photoreceptor cells in retinitis pigmentosa (RP) mice by inhibiting nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) signaling pathway. @*Methods@# (i) In vitro experiments, mouse retinal ganglion cells (661W cells) were divided into normal, model, LBP low-dose (LBP-L, 40 mg/L), LBP middle-dose (LBP-M, 80 mg/L), LBP high-dose (LBP-H, 160 mg/L), and positive drug control (NLRP3 inhibitor, 160 mg/L) groups. And the 661W cells were exposed to varying concentrations of H2O2 ranging from 50 to 400 μmol/L to determine the optimal concentration for inducing apoptosis (200 μmol/L). Then the cell viability was assessed using Cell Counting Kit-8 (CCK-8), while the apoptosis rate was detected by flow cytometry; the expression of NLRP3 was detected by immunofluorescence; and the expression of apoptosis markers was detected by enzyme-linked immunosorbent assay (ELISA) and Western blot (WB). (ii) In vivo assays were carried out with the use of C57/BL6 and Rd10 mice. The animal experimental groups were divided into normal, model, LBP-L, LBP-M, LBP-H, and NLRP3 inhibitor groups, in which the normal group was C57/BL6 mice and the other groups were Rd10 mice. Ten mice were included in each group, and the corresponding drugs were administered intragastrically for a duration of four weeks. NF-κB/NLRP3 pathway and the expression of apoptosis markers were observed by electroretinogram, histopathological examination, and WB to assess the effects of LBP on retinal photoreceptor cell apoptosis.@*Results@#(i) In vitro experiments, compared with the normal group, the apoptosis rate of 661W cells in model group was significantly increased (P < 0.01), and the expression levels of key proteins of NF-κB/NLRP pathway, such as NLRP3, NF-κB, p-NF-κB, and pro-apoptotic protein caspase-3, were up-regulated (P < 0.01). The rate of Bax/Bcl-2 was increased (P < 0.01), and the concentrations of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were significantly increased (P < 0.01). Compared with the model group, high dose of LBP decreased the apoptosis rate of 661W cells (P < 0.01), and down-regulated the expression levelsof the key proteins of NF-κB/NLRP3 pathway, including NF-κB, NLRP3, p-NF-κB, and caspase-3 (P < 0.01). The rate of Bax/Bcl-2 was decreased (P < 0.01), and the concentrations of IL-1β and TNF-α were decreased (P < 0.01). (ii) In vivo experiments, high dose of LBP significantly increased morphological changes in the outer nuclear layer (ONL) thickness of Rd10 mice, as well as functional changes in the amplitudes of the a-wave and b-wave (P < 0.01), which also down-regulated the expression levels of NF-κB (P < 0.05), NLRP3, p-NF-κB, and caspase-3 (P < 0.01), reduced the Bax/Bcl-2 rate (P < 0.01), and decreased the concentrations of IL-1β (P < 0.01) and TNF-α (P < 0.05). @*Conclusion@#LBP could improve both retinal morphology and function, providing protection to photoreceptors from apoptosis through the inhibition of the NF-κB/NLRP3 pathway.

Treatment of Retinitis Pigmentosa with Traditional Chinese and Western Medicine： A Review / 中国实验方剂学杂志

Retinitis pigmentosa （RP） is a group of progressive and blinding hereditary fundus diseases characterized by damaged retinal photoreceptor cells and retinal pigment epithelium. With the clinical manifestations of night blindness and progressive visual field defect， RP has a high possibility of developing into blindness， which seriously affects the quality of life of the patients. The recent years have witnessed increasing studies about the pathogenesis and treatment of RP. By reviewing the relevant articles， we conclude that the pathogenesis of RP is mainly related to genes， and retinal blood perfusion， oxidative stress injury， and inflammatory cascade all affect the progression of this disease. The traditional Chinese medicine （TCM） therapies for RP mainly include TCM compound prescriptions， Chinese medicine extract， acupuncture combined with medicine， and comprehensive TCM treatment. The Western medicine therapies include gene therapy， stem cell therapy， optogenetic therapy， retinal prosthesis， drugs， treatment of complications and other therapies. The intervention mechanisms of traditional Chinese and Western medicine often involve gene modification， alternative therapy， improvement of retinal blood perfusion， antioxidant damage， and nutritional support. By summarizing the specific methods and effects of traditional Chinese and Western medicine in treating RP， we hope to provide a reference for the management and treatment of RP.