Orbital histiocytosis; From A to Z.

PURPOSE: Histiocytosis is one of the most challenging diseases in medical practice. Because of the broad spectrum of clinical manifestations, systemic involvements, unknown etiology, and complex management, different types of histiocytosis are still a big question mark for us. Orbital histiocytosis is characterized by the abnormal proliferation of histiocytes in orbital tissues. It could affect the orbit, eyelid, conjunctiva, and uveal tract. Orbital histiocytosis can cause limited eye movement, proptosis, decreased visual acuity, and epiphora. In this study, we review the novel findings regarding the pathophysiology, diagnosis, and treatment of different types of histiocytosis, focusing on their orbital manifestations. METHOD: This review was performed based on a search of the PubMed, Scopus, and Embase databases or relevant published papers regarding orbital histiocytosis on October 9th, 2023. No time restriction was proposed, and articles were excluded if they were not referenced in English. RESULTS: 391 articles were screened, most of them being case reports. The pathophysiology of histiocytosis is still unclear. However, different mutations are found to be prevalent in most of the patients. The diagnostic path can be different based on various factors such as age, lesion site, type of histiocytosis, and the stage of the disease. Some modalities, such as corticosteroids and surgery, are used widely for treatment. On the other hand, based on some specific etiological factors for each type, alternative treatments have been proposed. CONCLUSION: Significant progress has been made in the detection of somatic molecular changes. Many case studies describe various disease patterns influencing the biological perspectives on different types of histiocytosis. It is necessary to continue investigating and clustering data from a broad range of patients with histiocytosis in children and adults to define the best ways to diagnose and treat these patients.

Clinical application of biomaterials in orbital implants: a systematic review.

PURPOSE: Various materials have been proposed for reconstructing orbital fractures. The materials used must meet certain criteria to ensure their suitability for restoring the structure and function of the organ. These criteria include biocompatibility, ease of application, non-toxicity, hypo-allergenicity, and non-carcinogenicity. In this study, we systematically reviewed the studies regarding the biomaterials in orbital implants and their clinical application. METHODS: A comprehensive search across various databases, including PubMed, Scopus, EMBASE, Cochrane Library, and Web of Science, was conducted until April 10th, 2023. After retrieving the search results and eliminating duplicates, final studies were included after screening through defined criteria. Human and animal studies assessing the clinical application of biomaterials in orbital implants were included. The quality of the case series and controlled intervention studies were evaluated using the NIH tool, and for animal studies, the risk of bias was assessed using SYRCLE's tool. RESULTS: Seventeen studies were included according to defined criteria. These studies aimed to explore the clinical application of biomaterials and examine the associated complications in orbital implants. CONCLUSION: We found that using biomaterials did not result in elevated intraocular pressure (IOP). However, we did observe certain complications, with infection, residual diplopia, and enophthalmos being the most frequently reported issues.

Validation and evaluation of school-based mental health literacy training program "The Guide Cymru" in Iranian adolescent students aged 13-15: study protocol.

BACKGROUND: Schools are an ideal setting for enhancing mental health literacy, a crucial strategy for improving adolescents' mental health knowledge and attitudes and promoting help-seeking. "The Guide Cymru" program is an adaptation of the mental health literacy program" The Guide" that was developed in Canada. The program will be culturally adapted for 13- to 15-year-old Iranian adolescent students in the first secondary schools. METHODS: In this randomized controlled trial, using the stratified random sampling procedure, the whole eighth and ninth grade student body (aged 13 to 15) from Sirjan City's first secondary schools will be included in the study. Twenty first secondary schools will be randomly assigned to one of two groups: control or intervention. Finally, 562 students and 40 teachers will participate in the research. The tools of mental health literacy scale (MHLs), mental health general knowledge and attitudes related to mental disorders/illnesses are employed in this study. DISCUSSION: This trial aims to be to explore whether "The Guide Cymru", a mental health literacy program offered to students as part of the school curriculum, can decrease the stigma associated with mental health and promote help-seeking behaviors among students.

Clinical effectiveness of combined whole body hyperthermia and external beam radiation therapy (EBRT) versus EBRT alone in patients with painful bony metastases: A phase III clinical trial study.

PURPOSE: To evaluate the response rate, pain relief duration, and time it took for pain to decline or resolve after radiation therapy (RT) with or without fever-range Whole Body Hyperthermia (WBH) in bony metastatic patients with mainly primary tumor of prostate and breast cancer leading to bone pain. MATERIALS & METHODS: Bony metastatic patients with pain score ≥4 on the Brief Pain Inventory (BPI) underwent RT of 30 Gy in 10 fractions in combination with WBH with nursing care under medical supervision versus RT-alone. WBH application time was 3-4 h in three fractions with at least 48-h intervals. All patients were stratified primary site, breast or prostate cancer vs others, BPI score, and exclusion criteria. The primary endpoint was complete response (CR) (BPI equal to zero with no increase of analgesics) within two months of follow-up. RESULTS: Based on this study, the RT-alone group showed the worst pain. The study was terminated after the enrollment of a total of 61 patients, 5 years after the first enrollment (April 2016 to February 2021). Finally, the CR rate in RT + WBH revealed the most significant difference with RT-alone, 47.4% versus 5.3% respectively within 2 months post-treatment (P-value <0.05). The time of complete pain relief was 10 days for RT + WBH, while the endpoint was not reached during the RT-alone arm. Pain progression or stable disease was observed in half of the patients in RT-alone group within 4 weeks after treatment. However, this score was near zero in RT + WBHT patients in two months post-treatment. CONCLUSIONS: WBH plus RT showed significant increases in pain relief and shorter response time in comparison with RT-alone for patients with bone metastatic lesions.

Hemicentral retinal vein occlusion in a patient with a history of coronavirus disease 2019 infection: a case report and review of the literature.

BACKGROUND: Considering the various manifestations of coronavirus disease 2019 and its imperative importance in terms of the right clinical approach and early management, we sought to present a hemicentral retinal vein occlusion case, with a history of heterozygosity of methylenetetrahydrofolate reductase (MTHFR) genes and potential for clotting complications as a late manifestation of coronavirus disease 2019, and provide a brief review of reported retinal vein occlusion cases in patients with coronavirus disease 2019. CASE PRESENTATION: A 35-year-old Iranian patient presented with a visual impairment in the left eye 4 months after recovering from coronavirus disease 2019. He reported a mild blurring of vision in the same eye a few days after admission due to coronavirus disease 2019. The ophthalmic evaluation was compatible with hemicentral retinal vein occlusion. Systemic and laboratory workups were negative except for borderline protein C activity, homocysteine levels, and heterozygosity of MTHFR genes. The patient was scheduled to receive three monthly intravitreal antivascular endothelial growth factor injections. CONCLUSION: We present a case of inferior hemicentral retinal vein occlusion case with an MTHFR mutation with sequential loss of vision 4 months after coronavirus disease 2019 to make clinicians aware of the possibility of late ocular coronavirus disease 2019 manifestations.

Vessel Density Features of Optical Coherence Tomography Angiography for Classification of Glaucoma Using Machine Learning.

PRCIS: Machine learning (ML) based on the optical coherence tomography angiography vessel density features with different thresholds using a support vector machine (SVM) model provides excellent performance for glaucoma detection. BACKGROUND: To assess the classification performance of ML based on the 4 vessel density features of peripapillary optical coherence tomography angiography for glaucoma detection. METHODS: Images from 119 eyes of 119 glaucoma patients and 76 eyes of 76 healthy individuals were included. Four vessel density features of optical coherence tomography angiography images were developed using a threshold-based segmentation method and were integrated into 3 models of machine learning classifiers. Images were divided into 70% training set and 30% test set. Classification performances of SVM, random forest, and Gaussian Naive Bayes models were evaluated with the area under the receiver operating characteristic curve (AUC) and accuracy. RESULTS: Glaucoma eyes had lower vessel densities at different thresholds. For differentiating glaucoma eyes, the best results were achieved with 70% and 100% thresholds, in which SVM classifier discriminated glaucoma from healthy eyes with an AUC of 1 and accuracy of 1. After SVM, the random forest classifier with 100% thresholds showed an AUC of 0.993 and an accuracy of 0.994. Furthermore, the AUC of our ML performance (SVM) was 0.96 in a subgroup analysis of mild and moderate glaucoma eyes. CONCLUSIONS: ML based on the combined peripapillary vessel density features of total vessels and capillaries in the whole image and ring image could provide excellent performance for glaucoma detection.

Artificial Intelligence and Infectious Keratitis: Where Are We Now?

Infectious keratitis (IK), which is one of the most common and catastrophic ophthalmic emergencies, accounts for the leading cause of corneal blindness worldwide. Different pathogens, including bacteria, viruses, fungi, and parasites, can cause IK. The diagnosis and etiology detection of IK pose specific challenges, and delayed or incorrect diagnosis can significantly worsen the outcome. Currently, this process is mainly performed based on slit-lamp findings, corneal smear and culture, tissue biopsy, PCR, and confocal microscopy. However, these diagnostic methods have their drawbacks, including experience dependency, tissue damage, cost, and time consumption. Diagnosis and etiology detection of IK can be especially challenging in rural areas or in countries with limited resources. In recent years, artificial intelligence (AI) has opened new windows in medical fields such as ophthalmology. An increasing number of studies have utilized AI in the diagnosis of anterior segment diseases such as IK. Several studies have demonstrated that AI algorithms can diagnose and detect the etiology of IK accurately and fast, which can be valuable, especially in remote areas and in countries with limited resources. Herein, we provided a comprehensive update on the utility of AI in IK.

Bilateral central serous retinal detachment in a patient with nephrotic syndrome: a case report.

BACKGROUND: The aim of this report is to highlight the importance of considering nephrotic syndrome as a potential underlying cause of bilateral central serous retinal detachment in a patient with systemic lupus erythematosus and to underscore the significance of a comprehensive systemic workup in these patients. CASE PRESENTATION: A 19-year-old Iranian female patient with history of systemic lupus erythematosus presented with progressive vision loss and bilateral macular elevation. Ophthalmic examination revealed periorbital edema, chemosis, and subretinal fluid at the macula of both eyes. Optical coherence tomography confirmed the existence of subretinal fluid and serous detachment located at the macula of both eyes. On fluorescein angiography, there were no signs of subretinal leakage such as smoke stack sign or expansile dot in late phases. Laboratory tests detected hypoalbuminemia and significant proteinuria, leading to the diagnosis of nephrotic syndrome. Treatment with prednisolone and albumin infusion resulted in improved visual acuity and resolution of subretinal fluid. CONCLUSION: Nephrotic syndrome can be a rare underlying cause of bilateral central serous retinal detachment, and its association with systemic lupus erythematosus should be considered. Hypoalbuminemia in nephrotic syndrome alters fluid dynamics in the retina, contributing to bilateral central serous retinal detachment. Early recognition and management of nephrotic syndrome are essential for vision recovery and preventing long-term complications.

Orbital histiocytosis and fibrohistiocytosis: the clinicopathological characteristics of 117 patients, over a decade of experience.

PURPOSE: To describe the clinicopathological features of a large cohort of patients with orbital histiocytoses and fibrohistiocytosis, such as Langerhans cell histiocytosis (LCH) and non-LCH disorders, and correlate patients' clinical characteristics with their pathological diagnosis. METHODS: In this retrospective study, medical records of patients presenting to Farabi Eye Hospital, a tertiary eye care center in Tehran, Iran, from 2010 until 2022, were reviewed. Patients' demographics, chief complaint, location and laterality of the tumor, best-corrected visual acuity, presence of bone erosion on imaging, and their pathological diagnosis were retrieved. Excisional biopsy was performed and evaluated through light microscopy and immunohistochemistry study for their respective markers, including CD1a, CD68, CD207, and S100. RESULTS: A total of 117 patients with 11 pathological subtypes of histiocytoses and fibrohistiocyosis were identified, with 56.4% male and 43.6% female patients. The mean age at presentation was 23.4 years (range 1.5 months-73 years). Swelling and palpable mass were the most common chief complaints. LCH was the most common pathology (32.5%), followed by juvenile xanthogranuloma (26.5%) and adult xanthogranuloma (21.4%). Age, lesion location, and bone erosion had a statistically significant difference among the various diagnosed subtypes. CONCLUSIONS: Histiocytoses and fibrohistiocytosis are diverse and rare disorders potentially involving multiple organ systems. Ophthalmic manifestations of these diseases are even more uncommon. We reviewed their orbital presentation along with their respective histopathological findings. Our results also suggested that an orbital CT scan can be of diagnostic value to discriminate LCH from other histiocytic pathologies.

Unusual orbital mucormycosis due to pecking injury: clinical characteristics and outcomes of four immunocompetent pediatric patients.

Mucormycosis is a serious fungal infection caused by fungi in the order of Mucorales. Orbital mucormycosis occurs more frequently in rhino-orbital, sino-orbital, and rhino-orbito-cerebral forms of the disease, while isolated orbital mucormycosis is much less common. Herein, we present four cases of immunocompetent children who developed primary cutaneous mucormycosis, which subsequently invaded and progressed to orbital mucormycosis following direct traumatic injury caused by pecking from Acridotheres tristis (Common Myna). Given the low prevalence of orbital mucormycosis in healthy children, an unknown source of infection and delayed diagnosis followed by late therapeutic interventions could result in life-threatening conditions and serious sequelae.

Short term choroidal microvascular changes following photodynamic therapy in chronic central serous chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSC) is characterized by focal serous detachment of the retina, primarily affecting the macula. Photodynamic therapy (PDT) is the best choice for treatment of chronic and recurrent patients. In this study we aim to evaluate the early effects of the half dose protocol (3 mg/m2 verteporfine) of PDT laser treatment on the micro vasculature of choroid. METHODS: Among thirty-one patients (62 eyes), twenty eyes were in the control group and forty-two eyes received PDT laser treatment. Vision log MAR, CMT (central macular thickness), SRF (sub retinal fluid), BCT (baseline choroidal thickness), CVI (choroidal vascular index), and laser treated area were compared between two groups. RESULTS: Results show that no strong correlation was detected between the impact of laser treatment and resolution of SRF in the first week in the fovea. The mean best corrected visual acuity (BCVA) of the patients significantly increased from 20/63 at the beginning of the study, according to the Snellen chart, to 20/49 in the first week and 20/38 in the sixth week. PDT can significantly reduce SRF and CMT in 6 weeks compared to the control group. Although there was initially a small, non-statistically significant increase in choroidal thickness and CVI after 1 week, a dramatic decrease occurs after 6 weeks. Therefore, after 6 weeks of PDT laser, all the indicators such as SRF, CMT, choroidal thickness, and CVI significantly reduced. CONCLUSION: PDT laser can significantly reduce SRF and CMT at 1 and 6 weeks and choroidal thickness and CVI at 6 weeks in chronic CSC patients. Also, a larger laser treated area has no impact on the final outcome. Therefore, it seems that the mechanism of PDT in CSC disease is the recovery of choriocapillaris circulation.

One-year outcomes of combined phacoemulsification and viscogoniosynechialysis with and without endoscopic cyclophotocoagulation in primary angle-closure glaucoma.

PURPOSE: To compare the outcomes of combined phacoemulsification and viscogoniosynechialysis (VGSL) with and without endoscopic cyclophtocoagulation (ECP) in primary angle-closure glaucoma (PACG). METHODS: In this prospective interventional case series 52 eyes of 50 patients were enrolled. Twenty-seven eyes underwent combined phacoemulsification and VGSL (PV group) and 25 eyes underwent the same procedure plus circumferential ECP (PVE group). All eyes were followed 1 day, 1 week, 3 months, 6 months, and 1 year after the procedure. Intraocular pressure and antiglaucoma medications were compared between and within groups using generalized estimating equations. Kaplan-Meier survival analysis was carried out to compare intensity to failure between groups. RESULTS: The mean ± SD age was 63.23 ± 6.87 years and 50% of the cases were male in the entire group. Intraocular pressure (IOP) and antiglaucoma medications were significantly reduced at all time points in comparison with the baseline in both groups (p < 0.05). There was no significant difference between groups in either IOP or medications at specific time points (p > 0.05). One eye in each group developed a fibrinous reaction in the postoperative period. There was no statistically significant difference between groups regarding the intensity to failure (P = 0.169). CONCLUSION: There were no significant differences in IOP and medication reduction between groups. Also, the complications were comparable between groups.

The effect of povidone-iodine 2% eye drops in the treatment of adenoviral keratoconjunctivitis.

BACKGROUND: Keratoconjunctivitis is one of the most common pathologies worldwide, caused by several infectious and noninfectious factors. This study aimed to determine the effect of povidone-iodine 2% eye drops in treating adenoviral keratoconjunctivitis. METHODS: This analytic cross-sectional study was conducted on patients referred to Farabi Eye Hospital Records of patients with adenoviral keratoconjunctivitis, more than 12 years of age, and no allergy to iodine who were treated by povidone-iodine 2% eye drops four times a day were assessed. Data included demographic characteristics, family history of adenoviral keratoconjunctivitis, follicular conjunctivitis, petechial conjunctival hemorrhages, periauricular lymphadenopathy, and the presence of conjunctival pseudomembrane were collected from the records. Discharge decrease, injection decrease, swelling decrease, pseudomembrane formation, periauricular lymphadenopathy, and subepithelial infiltration on the 7thday of assessment by physical examination were reported. RESULTS: Patients with a mean (±standard deviation) age of 33.77 (11.01) years were assessed. At the baseline, 95 (99.0%) follicular conjunctivitis, 94 (97.9%) petechial conjunctival hemorrhages, 29 (30.2%) periauricular lymphadenopathy, and 5 (5.2%) conjunctival pseudomembrane were recorded. On the 7thday of treatment, the discharge decreased in 92.7% of patients, and the injection decreased in 90.6%. The swelling decrease was also detected in 79.2% of patients. Subepithelial infiltration was only seen in 21.9% of the study population. Results showed that 2.1% of patients had periauricular lymphadenopathy, and only 13 out of 96 patients (13.5%) had pseudomembrane formation after 7 days. CONCLUSIONS: Based on the safety, availability, and tolerability of povidone-iodine and its promising effects on patients with adenoviral keratoconjunctivitis, further clinical trials assessing the impact of this drug in a longer duration of follow-up can be recommended.

Risk of secondary tumours in patients with non-metastatic and metastatic human retinoblastoma.

BACKGROUND: Retinoblastoma is an intraocular cancer in children and infants. Despite all the available treatment options and high survival rates in children with retinoblastoma, exposure to secondary tumours in adulthood is one of the concerns that physicians face. In many cases, dysfunction of the RB1 gene is the main cause of secondary tumours due to retinoblastoma. Therefore, the aim of this study was to evaluate the incidence of other secondary tumours in children with retinoblastoma. METHODS: In this regard, we performed continuous and integrated bioinformatics analyses to find genes, protein products, and signal pathways involved in other cancers. RESULTS: 1170 high-expression genes and 960 low-expression genes between non-invasive and invasive retinoblastoma were isolated. After examining the signal pathways, we observed bladder cancer and small cell lung cancer in the overexpressed genes. We also observed 5 cancers of endometriosis, prostate, non-small cell lung cancer, glioblastoma and renal cell carcinoma in low-expression genes. Based on the P-value index, non-small cell lung cancer, prostate and bladder cancers had the highest risk, and endometriosis cancer showed a lower probability of developing a secondary tumour in patients with retinoblastoma. In addition, the network between proteins also showed us that TP53, CDK2, SRC, MAPK1 proteins with high expression and JUN, HSP90AA1, and UBC proteins with low-expression play a significant role in candidate cancers. CONCLUSION: Lastly, we used continuous bioinformatics analysis to show that seven cancers are strongly linked to retinoblastoma cancer. Of course, more research is needed to find the best way to care for children who have been treated for retinoblastoma.

Magnetic NH2-MIL-101(Al)/Chitosan nanocomposite as a novel adsorbent for the removal of azithromycin: modeling and process optimization.

In the present study, the magnetic NH2-MIL-101(Al)/chitosan nanocomposite (MIL/Cs@Fe3O4 NCs) was synthesized and used in the removal of azithromycin (AZT) from an aqueous solution for the first time. The as-synthesized MIL/Cs@Fe3O4 NCs was characterized by SEM, TEM, XRD, FTIR, BET, and VSM techniques. The effect of various key factors in the AZT adsorption process was modeled and optimized using response surface methodology based on central composite design (RSM-CCD). The low value of p-value (1.3101e-06) and RSD (1.873) parameters, along with the coefficient of determination > 0.997 implied that the developed model was well fitted with experimental data. Under the optimized conditions, including pH: 7.992, adsorbent dose: 0.279 g/L, time: 64.256 min and AZT concentration: 10.107 mg/L, removal efficiency and AZT adsorption capacity were obtained as 98.362 ± 3.24% and 238.553 mg/g, respectively. The fitting of data with the Langmuir isotherm (R2: 0.998, X2: 0.011) and Pseudo-second-order kinetics (R2: 0.999, X2: 0.013) showed that the adsorption process is monolayer and chemical in nature. ΔH° > 0, ΔS° > 0, and ∆G° < 0 indicated that AZT removal was spontaneous and endothermic in nature. The effect of Magnesium on AZT adsorption was more complicated than other background ions. Reuse of the adsorbent in 10 consecutive experiments showed that removal efficiency was reduced by about 30.24%. The performance of MIL/Cs@Fe3O4 NCs under real conditions was also tested and promising results were achieved, except in the treatment of AZT from raw wastewater.

Herpetic endotheliitis and stromal keratitis following inactivated COVID-19 vaccination.

Given the scarcity of data regarding ocular complications following COVID-19 vaccination, the approach toward patients with suggestive symptoms and established clinical practice is lacking. Herein, we report the first case of herpetic endotheliithis and secondary stromal keratitis following inactivated COVID-19 vaccination who experienced a relapse due to poor adherence.

Utilization of health services among the elderly in Iran during the COVID-19 outbreak: A cross-sectional study.

Background and Aims: Elderly people are potentially vulnerable with a higher need for health services, and utilization of Essential Public Health Services (EPHS) among this group is of high importance. This study aimed to examine the utilization of health services among the elderly in Iran during the coronavirus disease 2019 outbreak. Methods: This was a cross-sectional study conducted in 21 public health centers in Sirjan, Southern Iran, from May to December 2020. A total of 420 elderly patients were selected through a systematic random sampling method. Data were collected using a questionnaire and were analyzed using SPSS v22.0. The binary logistic regression was used to examine the effect of demographic, socioeconomic and morbidity status on inpatient and outpatient healthcare utilization. Results: Our results showed that 56% of the elderly had a history of hospitalization during the last year. Although 60% of the elderly reported they had a perceived need for outpatient services, only 49% of them reported that they utilized outpatient services. 51% and 35.5% of the elderly reported that their inpatient and outpatient costs were covered by health insurance, respectively. Others reported their health spending was financed through out-of-pocket payments. Male gender aged 80 and above, urban residents, higher socioeconomic and supplemental insurance coverage were associated with an increase in health services utilization. The elderly with Cancer, mental disorders, kidney disease, and cardiovascular diseases (CVDs) were more likely to be hospitalized. Conclusion: There were demographic and socioeconomic inequalities in health services utilization among the elderly. Therefore, appropriate interventions and strategies are needed to reduce these inequalities in health services utilization among the elderly. In addition, given that the hospitalization rate was significantly higher among the elderly with chronic diseases than those without, it is crucial and necessary to take interventions to reduce the burden of chronic diseases in the future.

An integrative insight into the diversity, distribution, and biogeography of the freshwater endemic clade of the Ponticola syrman group (Teleostei: Gobiidae) in the Caucasus biodiversity hotspot.

Freshwater habitats of the Caucasus biodiversity hotspot represent a center of endemism for the gobiid genus Ponticola Iljin, 1927. Hitherto, large-scale molecular studies, owing to restricted taxon and geographical sampling, have failed to give an elaborate picture of diversity and evolutionary history of these species. Here, to contribute to filling this gap, we assessed taxonomic diversity, phylogeography and evolutionary history for the south Caspian populations of Ponticola presently classified as P. iranicus and P. patimari, using an integrative taxonomic approach comprising an entire geographic range sampling, and analyses of mitochondrial DNA haplotypes, the head lateral line system, otolith shape, and meristic and morphometric variation. All freshwater samples of the P. syrman group belong to a monophyletic clade with two main subclades: a small subclade confined to the upper Sefidroud sub-basin including the type locality of P. iranicus and a large subclade with three geographically constrained haplogroups (Hg1, Hg2, and Hg3), comprising the rest of the distribution. Hg1 showed an eastern distribution including the type locality of P. patimari, while Hg2 and Hg3 are sister groups with central and western-central distributions, respectively. The freshwater clade diverged from P. syrman during the Tyurkyanian low stand (~150 m b.s.l. lasting ~0.1 Myr), while the divergence of P. iranicus and P. patimari and radiations within P. patimari took place during the Bakunian high stand (up to 50 m a.s.l. lasting ~378-480 kya). Species delimitation analyses indicated two distinct species, corresponding to each main subclade. Although the otolith shape and lateral line analyses did not reflect with phylogeographic pattern, PCA and DFA plots of meristic and morphometric data showed a clear separation of the two major subclades corresponding to P. iranicus and P. patimari, suggesting the presence of significant morphological variation meriting formal taxonomic recognition. Overall, our findings (i) reveal the presence of two freshwater endemic species in the P. syrman group, and pending further investigation, hypothesize the presence of a third cryptic species; (ii) revise and document a narrow distributional range and low diversity for P. iranicus, in contrast to a wider distributional range and high diversity for P. patimari; (iii) suggest that the climatic oscillations of the Pleistocene were associated with the cladogenesis within the P. syrman group; and (iv) allowed for the recognition of conservation units and proposition of management measures.