Mitochondrial transplantation:a promising strategy for the treatment of retinal degenerative diseases

The retina,a crucial neural tissue,is responsible for transforming light signals into visual information,a process that necessitates a significant amount of energy.Mitochondria,the primary powerhouses of the cell,play an integral role in retinal physiology by fulfilling the high-energy requirements of photoreceptors and secondary neurons through oxidative phosphorylation.In a healthy state,mitochondria ensure proper visual function by facilitating efficient conversion and transduction of visual signals.However,in retinal degenerative diseases,mitochondrial dysfunction significantly contributes to disease progression,involving a decline in membrane potential,the occurrence of DNA mutations,increased oxidative stress,and imbalances in quality-control mechanisms.These abnormalities lead to an inadequate energy supply,the exacerbation of oxidative damage,and the activation of cell death pathways,ultimately resulting in neuronal injury and dysfunction in the retina.Mitochondrial transplantation has emerged as a promising strategy for addressing these challenges.This procedure aims to restore metabolic activity and function in compromised cells through the introduction of healthy mitochondria,thereby enhancing the cellular energy production capacity and offering new strategies for the treatment of retinal degenerative diseases.Although mitochondrial transplantation presents operational and safety challenges that require further investigation,it has demonstrated potential for reviving the vitality of retinal neurons.This review offers a comprehensive examination of the principles and techniques underlying mitochondrial transplantation and its prospects for application in retinal degenerative diseases,while also delving into the associated technical and safety challenges,thereby providing references and insights for future research and treatment.

Evaluation of retinal and choroidal thickness changes in overweight and obese adults without ocular symptoms by swept-source optical coherence tomography

AIM:To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography(SS-OCT).METHODS:According to the body mass index(BMI)results,the adults enrolled in the cross-sectional study were divided into the normal group(18.50≤BMI<25.00 kg/m^(2)),the overweight group(25.00≤BMI<30.00 kg/m^(2)),and the obesity group(BMI≥30.00 kg/m^(2)).The one-way ANOVA and the Chi-square test were used for comparisons.Pearson’s correlation analysis was used to evaluate the relationships between the measured variables.RESULTS:This research covered the left eyes of 3 groups of 434 age-and sex-matched subjects each:normal,overweight,and obesity.The mean BMI was 22.20±1.67,26.82±1.38,and 32.21±2.35 kg/m^(2) in normal,overweight and obesity groups,respectively.The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group(P<0.05 for all),while the retinal thickness of the three groups did not differ significantly.Pearson’s correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness,but no significant correlation was observed between BMI and retinal thickness.CONCLUSION:Choroidal thickness is decreased in people with overweight or obesity.Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.

Complications of Ziv-Aflibercept in Choroidal and Retinal Vascular Diseases

Introduction: The modern ophthalmology trends are changing rapidly every day with the introduction of much newer studies and research. Numerous anti-vascular endothelial growth factors (VEGF) are utilized as the mainstay in the treatment of intraocular vascular pathologies. The rationale of this study is to add to the literature regarding the safety and efficacy profile of the ziv-aflibercept as there is insubstantial data in patients with intraocular vascular pathologies being treated with this injection with prime focus on the complications of the injection. Materials and Methods: A prospective observational study was conducted at Opthalmology Department, Lahore General Hospital, Lahore between 14 August 2018 and 23 December 2019. Patients with choroidal and retinal vascular diseases like diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO) who had no active infection of eye and had no history of myocardial infarction or cerebrovascular accident were added in this study. Results: Best-corrected visual acuity was significantly improved at 4, 8, and 12 weeks as compared to the baseline (p Conclusion: The use of ziv-aflibercept injection via intravitreal route under aseptic conditions for choroidal and retinal vascular diseases is effective as well as safe with mild and treatable ocular side effects.

Impact of multifocal gas-permeable lens designs on short-term choroidal response, axial length, and retinal defocus profile

AIM:To investigate the impact of multifocal gas permeable contact lens(MFGPCL)in various add power and distance/near area allocation on short-term changes of choroidal thickness(ChT),axial length(AL),and retinal defocus profile in young adults.METHODS:Seventeen young adults(2 males and 15 females;age 23.17±4.48y)were randomly assigned to wear two designs binocularly with a one-week washout period in between.Total of four MFGPCL designs were assessed.All designs were distance-center that varied in two add power(+1.50 and 3.00 D)and/or two distance zone(DZ)diameters(1.50 and 3.00 mm;design A:DZ 1.5/add 3.0,B:DZ 1.5/add 1.5,C:DZ 3.0/add 3.0,D:DZ 3.0/add 1.5).ChT,AL,and peripheral refraction data were collected on each subject at baseline,on days 1 and 7 of MFGPCL daily wear.ChT was assessed in four quadrants using a spectraldomain optical coherence tomography.RESULTS:AL was shortened by-26±44μm with lens C,-18±27μm with lens D,-13±29μm with lens A,and-8±30μm with lens B(all P<0.05).A significant overall increase in ChT was observed with all 4 designs(lens A:+6±6μm,B:+3±7μm,C:+8±7μm,and D:+8±7μm).Temporal and superior choroid exhibited more choroidal thickening associated with MFGPCL.All designs induced significant relative peripheral myopia(RPM)beyond the central 20o across the horizontal meridian in both nasal and temporal fields(P<0.05).CONCLUSION:MFGPCLs show a significant influence on ChT and AL,which are associated with significant increase in RPM after short-term wear.The reliability and feasibility of quantifying short-term changes in ChT support its use as a promising marker for the long-term efficacy of myopia-controlling treatments.

Artificial intelligence in individualized retinal disease management

Owing to the rapid development of modern computer technologies,artificial intelligence(AI)has emerged as an essential instrument for intelligent analysis across a range of fields.AI has been proven to be highly effective in ophthalmology,where it is frequently used for identifying,diagnosing,and typing retinal diseases.An increasing number of researchers have begun to comprehensively map patients’retinal diseases using AI,which has made individualized clinical prediction and treatment possible.These include prognostic improvement,risk prediction,progression assessment,and interventional therapies for retinal diseases.Researchers have used a range of input data methods to increase the accuracy and dependability of the results,including the use of tabular,textual,or image-based input data.They also combined the analyses of multiple types of input data.To give ophthalmologists access to precise,individualized,and high-quality treatment strategies that will further optimize treatment outcomes,this review summarizes the latest findings in AI research related to the prediction and guidance of clinical diagnosis and treatment of retinal diseases.

Short-term fluctuation of intraocular pressure and influencing factors following intravitreal injection in patients with retinal vascular diseases

AIM:To investigate the patterns of short-term intraocular pressure(IOP)fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases.METHODS:Totally 81 patients were enrolled in this case control study.Eyes were categorized into 7 groups,including age-related macular degeneration(AMD),polypoidal choroidal vasculopathy(PCV),idiopathic choroidal neovascularization(CNV),proliferative diabetic retinopathy(PDR),diabetic macular edema(DME),macular edema secondary to branch(BVOME)and central(CVOME)retinal vein occlusion.IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively.Additionally,based on the administered medication,the eyes were classified into three treatment groups,including dexamethasone intravitreal implant(IVO),intravitreal conbercept(IVC),and intravitreal ranibizumab(IVR).To compare IOP values at various time points across groups,we employed one-way ANOVA,independent sample t-test or χ^(2) test and multivariate logistic regression analysis.RESULTS:Peak IOP values across all groups were observed at 40s,and 5min after intravitreal injection.Statistical differences in IOP were detected at the 5min among the 7 indication groups(F=2.50,P=0.029).When examing the impact of medications,the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups(P<0.001;P=0.007).The IOP values at 40s and 5min were significantly higher in BVOME and CVOME group compared to non-retinal vein occlusionsecondary macular edema(RVOME)group(P<0.001).Multivariate logistic regression analysis further confirmed that IOP measurement at 40s was significantly higher in CVOME group than in non-RVOME group(OR=1.64,95%CI:1.09-2.47;P=0.018).CONCLUSION:Needle size plays a crucial role in the transient changes of IOP following intravitreal injection.Before administering intravitreal injection to patients with central retinal vein occlusion,it is essential to exclude any underlysing causes of increased IOP.

Retinal nerve fiber layer defects and chronic kidney disease:the Kailuan Eye Study

AIM:To investigate whether retinal nerve fiber layer defects(RNFLDs)is a potential risk factor for chronic kidney disease(CKD)in Chinese adults.METHODS:The Kailuan Eye Study was a populationbased study that included 14440 participants.All participants underwent detailed assessments,RNFLDs were diagnosed using color fundus photographs.RESULTS:Overall,12507 participants[8533 males(68.23%)]had complete systemic examination data and at least one evaluable fundus photograph.RNFLDs were found in 621 participants[5.0%;95%confidence interval(CI):4.6%-5.34%],and 70 cases of multiple RNFLDs were found(11.27%).After adjusting multiple factors,RNFLDs was significantly associated with CKD severity,the ORs of CKD stage 3,stage 4 and stage 5 were 1.698,4.167,and 9.512,respectively.Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors,the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively.Furthermore,2294 participants had CKD(18.34%,95%CI:17.68%-18.99%).After adjusting for other factors,CKD presence was significantly correlated with the presence of RNFLDs.CONCLUSION:The strongest risk factors for RNFLDs are CKD and hypertension.Conversely,RNFLDs can be an ocular feature in patients with CKD.Fundoscopy can help detect systemic diseases,and assessment for RNFLDs should be considered in CKD patients.

Retinal capillary plexus in Parkinson’s disease using optical coherence tomography angiography

AIM:To evaluate the alterations of the retinal microvasculature and foveal avascular zone in patients with Parkinson’s disease(PD)using optical coherence tomography angiography(OCT-A).METHODS:A retrospective study of PD patients examined in the Ophthalmology Department of the General Hospital of Athens,“Georgios Gennimatas”from March 2021 to March 2022 was conducted.Totally 44 patients with PD were included and 18 healthy controls were examined,hence a total of 124 eyes were enrolled in the study.The foveal and parafoveal superficial and deep capillary plexus vascular density(fSCP-VD,fDCP-VD,pSCP-VD,pDCP-CD)and foveal avascular zone(FAZ)were quantified with OCTA.Optical coherence tomography(OCT)was used to measure macular thickness.Our statistical analysis was conducted by using a mixed effect linear regression model.RESULTS:After adjustment for age and gender,the mean parafoveal superficial capillary plexus vascular density(pSCP-VD)and mean parafoveal deep capillary plexus vascular density(pDCP-VD)were significantly decreased in individuals with PD(P<0.001 in both)by-2.35(95%CI-3.3,-1.45)and-7.5(95%CI-10.4,-4.6)respectively.fSCP-VD and fDCP-VD didn’t approach statistical significance.The FAZ area and perimeter were significantly decreased(P<0.001 in both)by-0.1 mm^(2)(95%CI-0.13,-0.07)and-0.49 mm^(2)(95%CI-0.66,-0.32)respectively.Circularity didn’t approach statistical significance.Central retinal thickness(CRT)was significantly decreased in individuals with PD(P<0.001)by-23.1μm(95%CI-30.2,-16)and temporal retinal thickness(TRT)was decreased(P=0.025)by-11μm(95%CI-22,-1.5)while nasal retinal thickness(NRT)only approached statistical significance(P=0.066).CONCLUSION:The mean pSCP-VD,pDCP-VD,CRT and TRT are significantly decreased and FAZ is altered in individuals with PD.These findings can be potentially used as biomarkers for the diagnosis and evaluation of early PD.

Melanin change of retinal pigment epithelium and choroid in the convalescent stage of Vogt-Koyanagi-Harada disease

AIM:To observe the melanin change of the retinal pigment epithelium(RPE)and choroid in the convalescent stage of Vogt-Koyanagi-Harada(VKH).METHODS:A retrospective study was performed on 40 eyes of 20 patients in the convalescent stage of VKH.Fundus photography(FP),multi-spectral imaging(MSI),and optical coherence tomography(OCT)were performed.RESULTS:In the VKH convalescent stage,focal RPE melanin accumulation(FRMA)was detected in 34 eyes(85%)on MSI and in 7 eyes(17.5%)on FP.FRMA was limited to the previous retinal detachment area in all 28 eyes(FRMA was detected in 34 eyes on MSI,which were enrolled,and 6 eyes lacked data in the acute stage).Sunset-glow fundus was detected in 20 eyes(50%)on FP.The mean density of FRMA in a 1-mm-diameter circular area of the fovea was 0.04±0.07 on MSI,which was significantly correlated with sunset-glow fundus(ρ=0.467,P=0.02).CONCLUSION:In the VKH convalescent stage,FRMA is derived from the RPE melanin change,and sunset-glow fundus is derived from the choroid melanin change.A higher density of FRMA in the fovea and sunset-glow fundus represents more serious depigmentation of melanin.

Therapeutic effect of microencapsulated porcine retinal pigmented epithelial cells transplantation on rat model of Parkinson's disease

Object To investigate the therapeutic effect of microencapsulated porcine retinal pigmented epithelial cells （RPE-M） transplantation on rat model of Parkinson＇s disease （PD）. Methods Primary porcine RPE cells were harvested by enzyme digestion and expanded in culture medium. Determine the levels ofdopamine （DA） and homovanillic acid （HVA） by high performance liquid chromatography electrochemical （HPLC） assay, and the levels of brain-derived neurotrophic factor （BDNF） and glial-derived neurotrophic factor （GDNF） were detected by ELISA. Alginate-polylysine-alginate （APA） microencapsulated cells were produced by using a high voltage electrostatic system. PD rat model was established by unilateral injection of 6-hydroxydopamine （6-OHDA） into the medial forebrain bundle （MFB）. After that, the RPE-M was transplanted into the corpus striatum of PD rat, and then the rotation test scores were recorded and biochemical changes of the corpus striatum were tested. Results The levels of DA, HVA, BDNF and GDNF secreted by RPE were stable in the RPE culture supernatant and were not changed by the microencapsulation. Eighty-three percent rats developed PD by unilateral lesion of 6-OHDA in the MFB. The RPE-M transplantation had therapeutic effect on 33% PD rats. Conclusion Porcine RPE cells grow actively in vitro and could secrete DA, HVA, BDNF, and GDNF constantly, which does not be affected by the passage culture and the APA miroencapsulation. RPE-M transplantation of may be a curative therapy for PD.

Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Bidirectional causality of physical exercise in retinal neuroprotection

Physical exercise is recognized as an effective intervention to improve mood,physical performance,and general well-being.It achieves these benefits through cellular and molecular mechanisms that promote the release of neuroprotective factors.Interestingly,reduced levels of physical exercise have been implicated in several central nervous system diseases,including ocular disorders.Emerging evidence has suggested that physical exercise levels are significantly lower in individuals with ocular diseases such as glaucoma,age-related macular degeneration,retinitis pigmentosa,and diabetic retinopathy.Physical exercise may have a neuroprotective effect on the retina.Therefore,the association between reduced physical exercise and ocular diseases may involve a bidirectional causal relationship whereby visual impairment leads to reduced physical exercise and decreased exercise exacerbates the development of ocular disease.In this review,we summarize the evidence linking physical exercise to eye disease and identify potential mediators of physical exercise-induced retinal neuroprotection.Finally,we discuss future directions for preclinical and clinical research in exercise and eye health.

Sickle cell retinopathy and systemic disease

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and mortality.Vascular occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and priapism.All ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell retinopathy.Proliferative sickle cell retinopathy(PSR)is the most common cause of vision loss.Untreated PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal detachment.Ophthalmic screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient outcomes.SCD patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic complications.While hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment options.Despite the United States screening all infants for SCD,there can be delays in diagnosis and treatment.This review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

Vitrectomy, lensectomy and silicone oil tamponade in the management of retinal detachment associated with choroidal detachment

AIM: To report the results of combined vitrectomy, lensectomy and silicone oil (SO) tamponade in treating primary rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). · METHODS: A retrospective, consecutive and case series study of 21 subjects with concurrent RRD associated with CD was conducted. All subjects underwent a standard three -port 20G pars plana vitrectomy (PPV) with lensectomy and silicone oil tamponade. Mean follow -up time was 8 months (rang from 4 to 19 months). The primary and final anatomic success rate, visual acuity and final intraocular pressure (IOP) were recorded and analyzed. ·RESULTS: Of 21 subjects, 8 were women and 13 were men. Age at presentation ranged from 22 to 75 years (mean 57.4 years). The presenting vision ranged from light perception to 0.15. The initial IOP ranged from 3mmHg to 12mmHg (mean 6.2mmHg). All eyes were phakic except one pseudophakic. No intraocular lens was implanted during the primary surgical intervention. Fifteen of 21 (71.4%) eyes had retina reattached after one operation. Six eyes had recurrent inferior retinal detachment due to proliferation. Five of them were successfully reattached after one or more additional operations. Mean IOP at final follow -up was 15.2mmHg (range from 8mmHg to 20mmHg). One case declined for further operation. The final reattachment rate was 95.2%. Visual acuity improved in 19 (90.5%) eyes, was unchanged in 1 (4.8%) eye and decreased in 1 (4.8%) eye.·CONCLUSION: Combination of vitrectomy, lensectomy and silicone tamponade is an effective method in treating RRD associated with CD, reducing the incidence of postoperative hypotony.

Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients

AIM： To comprehensively analyze the risk factors of rhegmatogenous retinal detachment （RRD） associated with choroidal detachment （CD）. METHODS： A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B -scan ultrasonography, and ultrasound biomicroscope （UBM）. Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment （RRDCD）. Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS： There were 52 eyes （19.62%） with CD. Pseudophakia was more commonly seen in RRDCD （21.15% ys6.10%, P=0.002）. Intraocular pressure （lOP） was lower （8.60 ±3.62 ys 12.96 ±3.55, P 〈0.001）, best - corrected visual acuity was worse [3.00 （2.00 to 3.00） vs 1.92 （1.22 to 3.00）, P=-0.001], and refractive error was more myopic [-4 （-9 to -2） vs -2 （-6 to 0）, P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment （P=0.007）. In RRDCD, 34.62% of eyes presented with multiple holes （P=0.044） and 25.00% with macular holes （P=0.012）, compared with 20.66% and 14.08% in R RD. High myopia （P=0.039）, low lOP （P=0.017）, and larger extent of retinal detachment （P〈0.001） were significant and independent risk factors for developing CD. - CONCLUSION： For CD in RRD, related factors include BCVA, lOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low lOP are significant and independent risk factors.

Effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness and retinal vessel diameter in branch retinal vein occlusion

AIM： To investigate the effects of two different doses of intravitreal bevacizumab on subfoveal choroidal thickness （SFChT） and retinal vessel diameter in patients with branch retinal vein occlusion. METHODS： An interventional, restrospective study of 41 eyes of 41 patients who had completed 12mo of follow-up, divided into group 1 （1.25 mg of bevacizumab, 21 eyes of 21 patients） and group 2 （2.5 mg of bevacizumab, 20 eyes of 21 patients）. Complete ophthalmic examination, fluorescein angiography, enhanced depth imaging optical coherence tomography and measurement of retinal vessel diameter with IVAN software were performed at baseline and follow-up. RESULTS： The SFChT changed from 279.1 （165-431） μm at baseline to 277.0 （149-413） μm at 12mo in group 1 （P= 0.086）, and from 301.4 （212-483） μm to 300.3 （199-514） μm in group 2 （P=0.076）. The central retinal arteriolar equivalent （CRAE） changed from 128.8 ±11.2 μm at baseline to 134.5±8.4 μm at 12mo in group 1, and from 134.6±9.0 μm to 131.4±12.7 μm in group 2 （P =0.767）. The central retinal venular equivalent （CRVE） changed from 204.1±24.4 μm at baseline to 196.3±28.2 μm at 12mo in group 1, and from 205.8±16.3 μm to 194.8±18.2 μm in group 2 （P=0.019）. The mean central macular thickness （P〈0.05） and average best-corrected visual acuity （BCVA; P〈0.05） improved in both groups CONCLUSION： Changes in the SFChT are not statistically significant and not different according to the doses of bevacizumab. The CRAE did not show significant change, however, the CRVE showed significant decrease regardless of the dose.

Choroidal thickness measurements with optical coherence tomography in branch retinal vein occlusion

AIM： To evaluate central macular thickness（CMT） and mean choroidal thickness（MCT） in eyes with branch retinal vein occlusion（BRVO）, before and after ranibizumab treatment using spectral domain-optical coherence tomography（SD-OCT）.·METHODS： Forty-two patients with unilateral BRVO and macular edema were included in this study. There were 25 men and 17 women. Using SD-OCT, choroidal thickness was measured at 500 μm intervals up to 1500μm temporal and nasal to the fovea. MCT was calculated based on the average of the 7 locations. All the eyes with BRVO were treated with intravitreal ranibizumab（0.5 mg/0.05 m L）. Comparisons between the BRVO and fellow eyes were analyzed using Mann-Whitney U test. Preinjection and post-injection measurements were analyzed using Wilcoxon test and repeated measure analysis.· RESULTS： At baseline, there was a significant difference between the BRVO and fellow eyes in MCT[BRVO eyes 245（165-330） μm, fellow eyes 229（157-327） μm]and CMT [BRVO eyes 463（266-899） μm, fellow eyes 235（148-378） μm（P =0.041, 0.0001, respectively）]. Following treatment, CMT [295（141-558） μm] and MCT [229（157-329） μm] decreased significantly compared to the baseline measurements（P =0.001, 0.006, respectively）.Also BCVA（log MAR） improved significantly（P=0.0001） in the BRVO eyes following treatment. After treatment CMT[BRVO eyes 295（141-558） μm, fellow eyes 234（157-351） μm]and MCT [BRVO eyes 229（157-329） μm, fellow eyes 233（162-286） μm] values did not reveal any significant difference in BRVO eyes and fellow eyes（P=0.051, 0.824,respectively）.· CONCLUSION： In eyes with BRVO, CMT and MCT values are greater than the fellow eyes, and decrease significantly following ranibizumab injection.

Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

Sectoral changes of the peripapillary choroidal thickness in patients with unilateral branch retinal vein occlusion

AIM: To investigate sectoral changes in the mean peripapillary choroidal thickness(PCT) in patients with unilateral branch retinal vein occlusion(BRVO). METHODS: This retrospective, interventional study included 41 patients with acute, unilateral BRVO without macular edema. All patients completed at least a 6-month follow-up period. The PCT was measured at eight locations(temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal). In addition to calculating the average of all locations, the peripapillary choroidal area was divided into four sectors: superior(average of superotemporal PCT, superior PCT, and superonasal PCT), temporal, inferior(average of inferotemporal PCT, inferior PCT, and inferonasal PCT), and nasal. RESULTS: In the BRVO-affected eyes, the mean PCT was 177.7±69.8 μm(range, 70.1-396.0 μm) at baseline and 127.8±54.8 μm(range, 56.4-312.1 μm) at 6 mo(P<0.001). In the non-affected contralateral eyes, the mean PCT was 192.5±60.6 μm(range, 61.4-365.0 μm) at baseline and 165.9±61.1 μm(range, 56.8-326.8 μm) at 6 mo(P<0.001). In sectoral analysis, the mean PCT in each sector was significantly reduced in over 6 mo in the BRVO-affected eyes(all P<0.001). In the non-affected contralateral eyes, the mean PCT was not significantly changed in any sector over the 6-month follow-up period(superior sector, P=0.143; temporal sector, P=0.825; inferior sector, P=0.192; and nasal sector, P=0.599).CONCLUSION: Sectoral analysis shows that the mean PCTs in all sectors are reduced significantly over 6 mo in the BRVO-affected eyes, but not in the non-affected contralateral eyes.

The role of Toll-like receptors in retinal ischemic diseases

Toll-like receptors（TLRs） are commonly referred to a series of evolutionary conserved receptors which recognize and respond to various microbes and endogenous ligands.Growing evidence has demonstrated that the expression of TLRs in the retina is regulated during retinal ischemic diseases,including ischemia-reperfusion injury,glaucoma,diabetic retinopathy（DR） and retinopathy of prematurity（ROP）.TLRs can be expressed in multiple cells in the retina,such as glial cells,retinal pigment epithelium（RPE）,as well as photoreceptor cells and endothelium cells.Activation of TLRs in retina could initiate a complex signal transduction cascade,induce the production of inflammatory cytokines and regulate the level of costimulatory molecules,which play prominent roles in the pathogenesis of retinal ischemic diseases.In this review,we summarized current studies about the relationship between TLRs and ischemic retinopathy.A greater understanding of the effect of TLRs on ischemic injuries may contribute to the development of specific TLR targeted therapeutic strategies in these conditions.