Surgical management of chronic sixth cranial nerve palsy: case report and literature review.

Background: Esotropia resulting from sixth cranial nerve palsy can substantially impact an individual's visual acuity and overall quality of life. If the condition does not resolve in 6-10 months, surgical intervention may be necessary. Various muscle surgeries may be considered, with vertical rectus muscle transposition emerging as the primary option for treatment of complete palsy. However, this technique carries the risk of anterior segment ischemia and post-surgery deviations. Herein, we present a successful treatment of chronic complete sixth nerve palsy using a modified Nishida procedure, without splitting or tenotomy, and an adjunct botulinum toxin A (BTA) injection in the ipsilateral medial rectus muscle. Case Presentation: A 59-year-old woman with a history of traumatic sixth nerve palsy had previously undergone horizontal muscle strabismus surgeries. Following multiple left medial rectus recessions, lateral rectus resection, and BTA injections, esotropia persisted. The worsening of her condition led to emotional distress and impaired social interaction. Initial examination revealed marked esotropia and limited left eye abduction. Magnetic resonance imaging (SIGNA MR750w, GE Healthcare, Waukesha, WI, USA) of the left eye revealed a contracted medial rectus muscle and substantial atrophy of the left lateral rectus muscle. A modified Nishida procedure was performed with an injection of 3 units of BTA into the ipsilateral medial rectus muscle, resulting in improved ocular alignment and stable findings after nine postoperative months. Furthermore, we supported our successful outcome with a summary of similar reported cases of sixth nerve palsy managed using the modified Nishida procedure with or without adjunctive procedures. Conclusions: Following the modified Nishida procedure, the patient experienced a reduction in diplopia, improved ocular alignment and stability, and an increased binocular diplopia-free field. This case underscores the importance of an individualized approach to complex strabismus cases and highlights the modified Nishida procedure as a valuable tool in such circumstances. In the future, strabismus management will focus on refining personalized treatment and exploring innovative techniques for complex cases. Our success in using a combination of Nishida procedure and BTA injection should be further investigated in large-scale studies.

Myopia trends among children and adolescents: a nationwide study in South Korea.

PURPOSE: To evaluate gender disparities in the progression of myopia among children and adolescents in South Korea. METHODS: Nationwide cross-sectional data of 1,190 subjects aged 10-18 years was obtained for the years of 2011 (baseline) and 2021 using the Korea National Health and Nutrition Examination Surveys. The prevalence of myopia, as well as data regarding age, household income, height, weight, body mass index, and age of menarche, were evaluated. Myopia was defined as a spherical equivalent (SE) ≤ -0.5 D. RESULTS: The prevalence of myopia among boys was stable in2021 compared to 2011, with rates of 53.7% and 52.8%, respectively (P = 0.372). Among girls, however, there was a statistically significant increase in myopia prevalence in 2021 compared to 2011, with rates of 73.7% and 51.6% (P < 0.001), respectively. Over 10 years, the adjusted prevalence ratio for myopia in boys was 1.11 (95% CI, 0.77-1.61), whereas myopia prevalence in girls underwent a 1.87-fold increase over the same period (95% CI, 1.30-2.69), and menarche at <12 years of age was associated with myopia in girls (PR = 0.84; 95% CI, 0.72-0.99). The spherical equivalent refraction in girls increased significantly over the same 10-year period, from -1.09 ± 0.13 D to -1.58 ± 0.17 D (P < 0.017), whereas in boys, there was no significant difference (P = 0.604). CONCLUSIONS: In our study cohort, the prevalence of myopia increased significantly among girls compared with boys over the course of decade. Additionally, an association between early menarche in girls and the prevalence of myopia was observed.

Effective low-cost pediatric vision screening by naive nonophthalmic examiners using the 'Arclight' device.

PURPOSE: To explore whether a low-cost ophthalmoscope (Arclight) can be used by naive nonophthalmic examiners to effectively screen for pediatric eye disease. METHODS: Fifty-four children (108 eyes) were examined by five medical students using an Arclight. Gold standard examination was performed by an ophthalmologist using a slit lamp and indirect ophthalmoscope. Examinations performed included ophthalmoscopy of the optic disc, estimation of the cup-to-disc ratio (CDR), corneal light reflex test (CRT), Bruckner's reflex test (BRT), and evaluation of refractive error. We determined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the nonophthalmologist's Arclight exam compared to the gold standard findings of comprehensive evaluation by pediatric ophthalmologists. RESULTS: Using the Arclight, the optic nerve exam was successfully completed in 65% of patients. CDRs above and below 0.5 could be determined with 66.7% sensitivity and 84.4% specificity. Arclight CRT measurements were significant (P < .00001) predictors of strabismus, with 80% sensitivity, 95.1%, specificity, 80% PPV, and 95.1% NPV. BRT was not a significant predictor of amblyopia, with a 34.6% sensitivity, 85.7% specificity, 69.2% PPV, and 58.5% NPV. Refractive error was estimated with a success rate of 81% for emmetropia, 38% for myopia, and 21% for hyperopia. The Arclight ease-of-use was rated on average as 4.4 (SD = 0.9) on a scale of 1 to 5, with 1 being the hardest and 5 being the easiest. CONCLUSIONS: Our study shows the Arclight as an affordable and effective alternative to the traditional ophthalmoscope for assessing eye disease in children. This device can improve eye health services in under-resourced regions.

Distribution and prevalence of refractive error in Iranian adult population results of the PERSIAN eye cohort study PECS.

The Persian Eye Cohort Study, a population-based cross-sectional study from 2015 to 2020, examined refractive error prevalence among 48,618 Iranian adults aged 31 to 70. The study encompassed six centers in Iran, employing random cluster sampling for demographic, medical, and socioeconomic data collection through interviews. Ophthalmic exams included visual acuity, automated and manual objective refraction, subjective refraction, slit lamp, and fundus examinations. Using the spherical equivalent definition, the sample population was categorized into groups. Results indicated a mean age of 49.52 ± 9.31 and a mean refractive error of 0.26 diopters (D) ± 1.6 SD (95% CI - 0.27 to -0.24), ranging from -26.1 to + 18.5 SD. Prevalence of myopia (< -0.5D) and hyperopia (> + 0.5D) was 22.6% (95% CI 22.2-23%) and 12.5% (95% CI 12.1-12.8%), respectively. Regarding different age groups, the prevalence of hyperopia and astigmatism exhibited a steady and significant rise with increasing age (p-value < 0.001 for both). The prevalence of Myopia, however, showed a distinctive pattern, initially increasing in adults under 45, declining in those aged 55-64, and rising again among individuals aged 60 and older. Female gender, older age, urban residency, higher education, higher income, and Fars ethnicity were significantly related to a higher prevalence of myopia (p-value < 0.001 for all). Female gender (p-value < 0.001), aging (p-value < 0.001), urban residency (p-value = 0.029), and lower-income (p-value = 0.005) were significantly related to higher prevalence of hyperopia. Astigmatism (> 1D) was prevalent in 25.5% of participants (95% CI 25.1-25.9%) and correlated with male gender, aging, urban residency, illiteracy, and higher income (p-value < 0.001, < 0.001, < 0.001, < 0.001, 0.014, respectively). The study's comparison with regional and international surveys highlighted the increase in myopia among those over 65 due to higher nuclear cataract rates in older adults. Myopia positively related to education, income, and urban residency, while hyperopia did not exhibit such associations.

UCI EyeMobile Exam Findings from School Children Following on-Site Screening.

Purpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss. Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency. Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), and amblyopia risk (14.4%). A majority (65.0%) of those examined received prescription spectacles from UCI EyeMobile, with around a third requiring a new or updated prescription. The frequency of REs and amblyopia and the spectacle prescription rate were uniform across OC congressional districts. Myopia and amblyopia risk was positively and negatively associated with household income, respectively. Conclusion: The UCI EyeMobile for Children serves as a vital vision care program, providing free vision screening, comprehensive eye examinations, and spectacles. A significant number of children required examination, and a high frequency of REs and amblyopia were detected in examined children, with subsequent provision of prescription spectacles to most children.

Pediatric refractive surgery: current opinion in ophthalmology.

PURPOSE OF REVIEW: Pediatric refractive surgery has been growing at a steady pace since its introduction in the early 1980 s. This article will review common laser refractive surgeries performed on pediatric patients along with controversies regarding the practice. RECENT FINDINGS: Pediatric refractive surgery is reserved for a small population of children who fail amblyopic treatment due to high anisometropic refractive errors. Publications over the years have treated these children with various types of laser refractive surgery. SUMMARY: Laser pediatric refractive surgery appears to be well tolerated and effective for the population of children that need it. It provides an alternative for anisometropic amblyopia treatment for children who would have otherwise not been able to improve their vision.

An Update to Biomechanical and Biochemical Principles of Retinal Injury in Child Abuse.

Abusive head trauma (AHT) is an extreme form of physical child abuse, a subset of which is shaken baby syndrome (SBS). While traumatic injury in children is most readily observed as marks of contusion on the body, AHT/SBS may result in internal injuries that can put the life of the child in danger. One pivotal sign associated with AHT/SBS that cannot be spotted with the naked eye is retinal injury (RI), an early sign of which is retinal hemorrhage (RH) in cases with rupture of the retinal vasculature. If not addressed, RI can lead to irreversible outcomes, such as visual loss. It is widely assumed that the major cause of RI is acceleration-deceleration forces that are repeatedly imposed on the patient during abusive shaking. Still, due to the controversial nature of this type of injury, few investigations have ever sought to delve into its biomechanical and/or biochemical features using realistic models. As such, our knowledge regarding AHT-/SBS-induced RI is significantly lacking. In this mini-review, we aim to provide an up-to-date account of the traumatology of AHT-/SBS-induced RI, as well as its biomechanical and biochemical features, while focusing on some of the experimental models that have been developed in recent years for studying retinal hemorrhage in the context of AHT/SBS.

Exploring Pediatric Vision Care: Insights from Five Years of Referral Cases in the UCI Eye Mobile and Implications of COVID-19.

PURPOSE: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses. RESULTS: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age (P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender (P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years (P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76). CONCLUSIONS: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XXX-XXX.].

The Traces of Dysregulated lncRNAs-Associated ceRNA Axes in Retinoblastoma: A Systematic Scope Review.

PURPOSE: Long non-coding RNAs are an essential component of competing endogenous RNA regulatory axes and play their role by sponging microRNAs and interfering with the regulation of gene expression. Because of the broadness of competing endogenous RNA interaction networks, they may help investigate treatment targets in complicated disorders. METHODS: This study performed a systematic scoping review to assess verified loops of competing endogenous RNAs in retinoblastoma, emphasizing the competing endogenous RNAs axis related to long non-coding RNAs. We used a six-stage approach framework and the PRISMA guidelines. A systematic search of seven databases was done to locate suitable papers published before February 2022. Two reviewers worked independently to screen articles and collect data. RESULTS: Out of 363 records, fifty-one articles met the inclusion criteria, and sixty-three axes were identified in desired articles. The majority of the research reported several long non-coding RNAs that were experimentally verified to act as competing endogenous RNAs in retinoblastoma: XIST/NEAT1/MALAT1/SNHG16/KCNQ1OT1, respectively. At the same time, around half of the studies investigated unique long non-coding RNAs. CONCLUSIONS: Understanding the many features of this regulatory system may aid in elucidating the unknown etiology of Retinoblastoma and providing novel molecular targets for therapeutic and clinical applications.

Pigmented pyogenic granuloma of the cornea and conjunctiva: a rare bilateral presentation.

Pyogenic granuloma, also known as lobular capillary hemangioma, is a benign vascular lesion that primarily affects the skin and mucous membranes. It is not pyogenic; nor is it granulomatous. It typically arises in response to local trauma or surgery, irritation, hormonal changes, or chronic inflammation, and it sometimes occurs spontaneously. The occurrence of pigmented pyogenic granuloma in the conjunctiva and cornea without any history of trauma or surgery is extremely rare, particularly in children. We report the clinical presentation, diagnostic evaluation, and successful management of bilateral biopsy-proven conjunctival and corneal pigmented isolated pyogenic granuloma in an 11-year-old girl. No signs of recurrence were seen at the 3-months follow-up.

Deep Learning Approach for Differentiating Etiologies of Pediatric Retinal Hemorrhages: A Multicenter Study.

Retinal hemorrhages in pediatric patients can be a diagnostic challenge for ophthalmologists. These hemorrhages can occur due to various underlying etiologies, including abusive head trauma, accidental trauma, and medical conditions. Accurate identification of the etiology is crucial for appropriate management and legal considerations. In recent years, deep learning techniques have shown promise in assisting healthcare professionals in making more accurate and timely diagnosis of a variety of disorders. We explore the potential of deep learning approaches for differentiating etiologies of pediatric retinal hemorrhages. Our study, which spanned multiple centers, analyzed 898 images, resulting in a final dataset of 597 retinal hemorrhage fundus photos categorized into medical (49.9%) and trauma (50.1%) etiologies. Deep learning models, specifically those based on ResNet and transformer architectures, were applied; FastViT-SA12, a hybrid transformer model, achieved the highest accuracy (90.55%) and area under the receiver operating characteristic curve (AUC) of 90.55%, while ResNet18 secured the highest sensitivity value (96.77%) on an independent test dataset. The study highlighted areas for optimization in artificial intelligence (AI) models specifically for pediatric retinal hemorrhages. While AI proves valuable in diagnosing these hemorrhages, the expertise of medical professionals remains irreplaceable. Collaborative efforts between AI specialists and pediatric ophthalmologists are crucial to fully harness AI's potential in diagnosing etiologies of pediatric retinal hemorrhages.

Modified horizontal muscle transposition without tenotomy and splitting for a case of inferior rectus and inferior oblique muscles aplasia with hemifacial microsomia.

Aplasia of the inferior rectus and inferior oblique muscles is extremely rare. Failure of the normal embryologic development of the inferior mesodermal complex can lead to agenesis of inferior rectus, inferior oblique, and lower sections of the lateral rectus muscles. This rare condition is usually seen in association with craniofacial syndromes or in conjunction with microcornea, microphthalmos, Axenfeld-Rieger syndrome, and coloboma. The usual treatment for this condition is a reverse Knapp procedure to improve the vertical alignment; however, this procedure can lead to complications, such as anterior segment ischemia, undercorrection, and torsional problems. To our knowledge, unilateral inferior rectus and inferior oblique muscle aplasia has not been described previously in a patient with congenital facial nerve palsy and optic nerve hypoplasia. In the present case, the patient was successfully treated with a modified minimally invasive horizontal rectus muscle transposition procedure.

Arteritic Anterior Ischemic Optic Neuropathy (AAION) Associated with COVID-19 Infection: A Case Report and Review of the Literature.

Anterior ischemic optic neuropathy (AION) is the most frequent cause of acute optic nerve damage in the elderly, usually causing acute, unilateral, and painless permanent visual loss. Arteritic anterior ischemic optic neuropathy (AAION) is a result of endothelial cell inflammation and the subsequent thrombosis and occlusion in the blood-supplying arteries of the optic nerve head. AAION accounts only for 5-10% of all AION cases that are associated with vasculitis which usually takes place in the course of a giant cell arteritis (GCA). In this paper, we report a case of AAION following a COVID-19 respiratory infection. Although it is uncertain whether SARS-CoV-2 infection triggered the AAION or was coincidental, the possible association of the events is concerning.

Promotor methylation in ocular surface squamous neoplasia development: epigenetics implications in molecular diagnosis.

INTRODUCTION: Cancer is heavily influenced by epigenetic mechanisms that include DNA methylation, histone modifications, and non-coding RNA. A considerable proportion of human malignancies are believed to be associated with global DNA hypomethylation, with localized hypermethylation at promoters of certain genes. AREA COVERED: The present review aims to emphasize on recent investigations on the epigenetic landscape of ocular surface squamous neoplasia, that could be targeted/explored using novel approaches such as personalized medicine. EXPERT OPINION: While the former is thought to contribute to genomic instability, promoter-specific hypermethylation might facilitate tumorigenesis by silencing tumor suppressor genes. Ocular surface squamous neoplasia, the most prevalent type of ocular surface malignancy, is suggested to be affected by epigenetic mechanisms, as well. Although the exact role of epigenetics in ocular surface squamous neoplasia has mostly been unexplored, recent findings have greatly contributed to our understanding regarding this pathology of the eye.

Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review.

Background: It is becoming more and more apparent that Grave's Ophthalmopathy (GO) pathogenesis may be aided by epigenetic processes such as DNA methylation modifications, histone tail covalent modifications, and non-coding RNA (ncRNA)-based epigenetic processes. In the present study, we aimed to focus more on the miRNAs rather than lncRNAs due to lack of investigations on these non-coding RNAs and their role in GO's pathogenesis. Methods: A six-stage methodology framework and the PRISMA recommendation were used to conduct this scoping review. A comprehensive search was conducted across seven databases to discover relevant papers published until February 2022. The data extraction separately, and quantitative and qualitative analyses were conducted. Results: A total of 20 articles were found to meet inclusion criteria. According to the results, ncRNA were involved in the regulation of inflammation (miR-146a, LPAL2/miR-1287-5p axis, LINC01820:13/hsa miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis), regulation of T cell functions (miR-146a/miR-183/miR-96), regulation of glycosaminoglycan aggregation and fibrosis (miR-146a/miR-21), glucocorticoid sensitivity (miR-224-5p), lipid accumulation and adipogenesis (miR-27a/miR-27b/miR-130a), oxidative stress and angiogenesis (miR-199a), and orbital fibroblast proliferation (miR-21/miR-146a/miR-155). Eleven miRNAs (miR-146a/miR-224-5p/miR-Let7d-5p/miR-96-5p/miR-301a-3p/miR-21-5p) were also indicated to have the capacity to be used as biomarkers. Conclusions: Regardless of the fact that there is significant documentation of ncRNA-mediated epigenetic dysfunction in GO, additional study is needed to thoroughly comprehend the epigenetic connections concerned in disease pathogenesis, paving the way for novel diagnostic and prognostic tools for epigenetic therapies among the patients.

An update in the applications of exosomes in cancer theranostics: from research to clinical trials.

Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.

PERSIAN Eye Cohort Study (PECS): Design, Methodology.

BACKGROUND: To report the study protocol, methodology and latest enrollment data of a large epidemiological multi-central eye cohort named PERSIAN Eye Cohort Study (PECS), originating from the ongoing PERSIAN Cohort Study, to investigate the distribution of ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. METHODS: A central committee designed the study and equipped six chosen centers (Khameneh, Some'e Sara, Hoveizeh, Yazd, Rafsanjan and Zahedan). A focal point in each center conducted the study under close supervision of the central committee. RESULTS: This ongoing study was launched in 2014. Out of 65,580 eligible participants of the PERSIAN Cohort, 48,618 individuals aged 35-70 have been enrolled in the PECS (response rate: 74.13%) until June 2021. Slit lamp and fundus photography were performed for 28,702 (59.03%) and 27,437 (56.43%) individuals, respectively. CONCLUSION: This large epidemiological multi-central eye cohort can improve our epidemiological knowledge of the prevalent ophthalmic disorders in different regions and ethnicities of Iran, and determine their associations with various exposures of ophthalmic and non-ophthalmic nature. This will be very useful for future planned nationwide and global interventions.

Intravitreal injection of methotrexate in persistent diabetic macular edema: a 6-month study.

Background: Diabetic macular edema (DME) affects approximately 10% of patients with diabetes mellitus. This condition can cause blurred or distorted vision, which significantly affects the quality of life of these patients. We evaluated the therapeutic effects of intravitreal methotrexate (MTX) injections on persistent DME. Methods: This prospective interventional case series included patients with confirmed persistent DME that was unresponsive to previous standard treatments. The patients underwent comprehensive eye examinations and macular imaging with optical coherence tomography (OCT). A single intravitreal MTX injection (400 µg MTX in 0.16 mL solution) was administered, followed by patient assessments at 1, 3, and 6 months after injection. Best-corrected distance visual acuity (BCDVA), intraocular pressure (IOP), macular thickness (MT), and central subfield thickness (CST) were measured at baseline and post-injection to evaluate treatment efficacy. Results: We included 33 eyes of 30 patients with a mean (standard deviation [SD], range) age of 62.7 (8.3, 44 to 77) years, of whom 17 (56.7%) were men and 13 (43.3%) were women. All participants had type 2 diabetes mellitus, with a mean (SD, range) duration of 17.0 (6.8, 10 to 31) years. Most participants (n = 27 eyes, 81.8%) had non-proliferative diabetic retinopathy, and six eyes (18.2%) had regressed proliferative diabetic retinopathy. Four eyes (12.1%) had undergone prior macular laser photocoagulation. The mean (SD) number of prior intravitreal bevacizumab injections was 3.4 (0.8), and 29 eyes (87.8%) had received one intravitreal triamcinolone injection. During the study period, a statistically significant difference was observed in CST (P < 0.05); however, no statistically significant differences were observed in BCDVA, MT, or IOP (P > 0.05). Pairwise comparison revealed a significant decrease in CST at 6 months post-injection compared to the baseline value (P < 0.05). During the investigation period, no side effects of MTX, such as macular edema, retinal tears, vitreous hemorrhage, endophthalmitis, or vision loss, were observed. Conclusions: A single intravitreal MTX injection significantly reduced CST in patients with persistent DME, without relevant safety concerns. However, no significant improvement in functional outcomes was observed. Therefore, there is no strong evidence to recommend its use as a treatment for pDME. Further studies, preferably randomized clinical trials with long-term follow-ups, are warranted to assess the long-term efficacy, safety, and potential benefits of intravitreal MTX for the treatment of persistent DME.