Optical Coherence Tomography Features of Tuberculous Serpiginous-like Choroiditis and Serpiginous Choroiditis

Objective To investigate optical coherence tomography（OCT） characteristics of tuberculous serpiginous-like choroiditis（Tb-SLC） and serpiginous choroiditis（SC） and to perform OCT to differentiate between these conditions.Methods This retrospective,case-control study examined consecutively enrolled patients with active Tb-SLC or SC.Patients underwent comprehensive ocular examinations and imaging（OCT,color fundus photography,autofluorescence imaging,fluorescein angiography,and indocyanine green angiography）.Findings were examined and compared between eyes with SC and Tb-SLC.Results Nine patients with active Tb-SLC（14 eyes） and 8 with active SC（12 eyes） were included.The following OCT findings were observed significantly more often in the Tb-SLC group than in the SC group： vitreal hyper-reflective spots [5 Tb-SLC eyes（36%）,no SC eyes：P = 0.02],intraretinal edema [11 Tb-SLC eyes（79%）,3 SC eyes（25%）：P = 0.01],sub-retinal pigment epithelium（RPE） drusenoid deposits [11 Tb-SLC eyes（79%）,2 SC eyes（17%）：P 〈 0.01],and choroidal granulomas [8 Tb-SLC eyes（57%）,2 SC eyes（17%）：P = 0.03].A hyporeflective,wedge-shaped band was observed more often in the SC group [5 Tb-SLC eyes（36%）,9 SC eyes（75%）：P = 0.045] than in the Tb-SLC group.The incidence of other OCT signs did not differ between the groups and included outer nuclear layer hyper-reflection,outer retinal tabulation,and choriocapillaris point-like hyper-reflection.Conclusion Vitreal hyper-reflective spots,intraretinal fluid,sub-RPE drusenoid deposits,and choroidal granulomas on OCT images may indicate Tb-SLC.Additionally,a hyporeflective,wedge-shaped band may indicate SC.Therefore,OCT is likely helpful in differentiating between Tb-SLC and SC.

Efficacy of Anti-VEGF and Subtenon Injection of Triamcinolone Acetonide for Choroidal Neovascularization Associated with Multifocal Choroiditis

Purpose: To evaluate the short-term efficacy of intravitreal anti-VEGF (Lucentis) and sub-tenon injection of triamcinolone acetonide for choroidal neovascularization (CNV) associated with multifocal choroiditis (MC). Methods: Eight eyes of 8 patients treated with intravitreal anti-VEGF and posterior sub-tenon injection of Triamcinolone Acetonide (TA) for subfoveal or juxtafoveal CNV associated with MC were retrospectively reviewed. Best corrected visual acuity (BCVA), results of fundus fluorescein angiography (FFA)/indocyanine green angiography (ICGA), optical coherence tomography (OCT) at baseline and 3, 6 months after treatment were compared. Results: All of the 8 patients showed significant improvement in BCVA at 3 and 6 months after treatment (P < 0.05). FFA/ICGA showed decrease or cessation of inflammation in 8 patients (100%). 7 patients (87.5%) had no significant active leakage while 1 patient (12.5%) had persistent leakage from the neovascular lesion at 3-month follow up. 6 months after treatment, no recurrence of inflammation occurred and no active leakage in all 8 patients. OCT showed reduced CNV area and alleviated edema. There are no severe treatment-related side effects expect slight eye pain during infusion in one patient. Intraocular pressure was all normal in follow up. Conclusion: Although the follow-up time and the number of patients in this study were limited, the use of intravitreal anti-VEGF combined with sub-tenon injection of TA was associated with improvement of visual acuity in patients with CNV secondary to MC. Further studies including a greater number of patients with longer follow up time are needed.

Clinical features and possible pathogenesis of multiple evanescent white dot syndrome with different retinal diseases and events:a narrative review

●Multiple evanescent white dot syndrome(MEWDS)is a rare fundus disease,characterized by acute vision loss and visual field defects.Many previous studies have explained the possible pathogenesis and clinical features of primary MEWDS.However,as the number of reported cases increases,secondary MEWDS occurs in other related retinal diseases and injuries,exhibiting some special characteristics.The associated retinal diseases include multifocal choroiditis/punctate inner choroidopathy(MFC/PIC),acute zonal occult outer retinopathy,best vitelliform macular dystrophy,pseudoxanthoma elasticum,and ocular toxoplasmosis.The related retinal injury is laser photocoagulation,surgery,and trauma.Although primary MEWDS often have a self-limiting course,secondary MEWDS may require treatment in some cases,according to the severity of concomitant diseases and complications.Notably,MEWDS secondary to MFC/PIC that is prone to forming choroidal neovascularization and focal choroidal excavation,needs positive treatment with corticosteroids.The possible underlying pathogenesis of secondary MEWDS is the exposure of choroidal antigen after the disruption of Bruch’s membrane.The MEWDS-related features in secondary MEWDS are still evanescent under most circumstances.Its prognosis and treatment depend on the severity of complications.Current studies propose that the etiology is associated with immune factors,including viral infection,inflammation in choroid and Bruch’s membrane,and antigen exposure caused by retinal and/or choroidal insults.More pathogenic studies should be conducted in the future.Accurate diagnosis for secondary MEWDS could benefit patients in aspects of management and prognosis.

Ocular syphilis:a case series of four patients and a review of the literature

Background:The incidence of syphilis has been increasing in the United States over the last two decades,with a more recent increase among women.Ocular syphilis is an uncommon but important complication of syphilis,most often presenting as posterior or panuveitis in late or latent syphilis of unknown duration.Untreated ocular syphilis may lead to permanent vision loss,underscoring the importance of appropriate evaluation and treatment of ocular syphilis.Case Description:In a retrospective,non-contiguous case series,we highlight four patients diagnosed and treated with ocular syphilis at a single institution.Four presentations of ocular syphilis are illustrated:anterior and intermediate uveitis,optic neuritis,posterior uveitis,and panuveitis.All patients initially presented with a decreased visual acuity(VA).One patient had a previous diagnosis of human immunodeficiency virus(HIV).Three patients were treated with intravenous(IV)penicillin and one patient with IV ceftriaxone.All had a return to their baseline VA after their course of treatment.Conclusions:Syphilis may go undetected without a high index of clinical suspicion due to its nonspecific presentations.All patients with ocular inflammation should have syphilis testing as a part of their infectious workup with both treponemal and non-treponemal testing.Patients diagnosed with syphilis and are not known to be HIV-negative should undergo testing for HIV due to the high rate of co-infection.Early diagnosis and prompt treatment after onset of symptoms may contribute to a more favorable prognosis for ocular syphilis.

Using choroidal thickness to detect myopic macular degeneration

AIM:To explore the usage of choroidal thickness measured by swept-source optical coherence tomography(SS-OCT)to detect myopic macular degeneration(MMD)in high myopic participants.METHODS:Participants with bilateral high myopia(≤−6 diopters)were recruited from a subset of the Guangzhou Zhongshan Ophthalmic Center-Brien Holden Vision Institute High Myopia Cohort Study.SS-OCT was performed to determine the choroidal thickness,and myopic maculopathy was graded by the International Meta-Analysis for Pathologic Myopia(META-PM)Classification.Presence of MMD was defined as META-PM category 2 or above.RESULTS:A total of 568 right eyes were included for analysis.Eyes with MMD(n=106,18.7%)were found to have older age,longer axial lengths(AL),higher myopic spherical equivalents(SE),and reduced choroidal thickness in each Early Treatment Diabetic Retinopathy Study(ETDRS)grid sector(P<0.001).The area under the receiver operating characteristic(ROC)curves(AUC)for subfoveal choroidal thickness(0.907)was greater than that of the model,including age,AL,and SE at 0.6249,0.8208,and 0.8205,respectively.The choroidal thickness of the inner and outer nasal sectors was the most accurate indicator of MMD(AUC of 0.928 and 0.923,respectively).An outer nasal sector choroidal thickness of less than 74μm demonstrated the highest odds of predicting MMD(OR=33.8).CONCLUSION:Choroidal thickness detects the presence of MMD with high agreement,particularly of the inner and outer nasal sectors of the posterior pole,which appears to be a biometric parameter more precise than age,AL,or SE.

Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

Mechanism of Cu entry into the brain:many unanswered questions

Brain tissue requires high amounts of copper(Cu)for its key physiological processes,such as energy production,neurotransmitter synthesis,maturation of neuropeptides,myelination,synaptic plasticity,and radical scavenging.The requirements for Cu in the brain vary depending on specific brain regions,cell types,organism age,and nutritional status.Cu imbalances cause or contribute to several life-threatening neurologic disorders including Menkes disease,Wilson disease,Alzheimer’s disease,Parkinson’s disease,and others.Despite the well-established role of Cu homeostasis in brain development and function,the mechanisms that govern Cu delivery to the brain are not well defined.This review summarizes available information on Cu transfer through the brain barriers and discusses issues that require further research.

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.

Non-linear relationship between age and subfoveal choroidal thickness in Chinese patients with proliferative diabetic retinopathy

BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness(SFCT)in proliferative diabetic retinopathy(PDR).AIM To investigate the relationship between the SFCT and age in Chinese patients with PDR.METHODS This was a cross-sectional retrospective study.The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR.Contralateral eyes that met the criteria were included in the study.All necessary laboratory tests were performed at the time of admission.Central macular thickness(CMT)and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography.CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software.RESULTS The final analysis included a total of 234 individuals with PDR.The average age was 55.60 years old±10.03 years old,and 57.69%of the population was male.Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR[β=-2.44,95%confidence interval(95%CI):-3.46 to-1.42;P<0.0001].In the fully adjusted model,the correlation between SFCT and age remained steady(β=-1.68,95%CI:-2.97 to-0.39;P=0.0117).Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear,with an inflection point at 54 years of age.CONCLUSION Our findings suggest that age is a key determinant of choroidal thickness.The non-linear link between SFCT and age in PDR patients should be taken into account.

An efficacy analysis of anti-vascular endothelial growth factor therapy for choroidal neovascularization secondary to multifocal choroiditis and comparison with wet age-related macular degeneration

Objective： To evaluate the effect of anti-vascular endothelial growth factor （VEGF） on juxtafoveal choroidal neovascularization （CNV） secondary to multifocal choroiditis （MFC） and wet age-related macular degeneration （AMD）. Methods： In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups： 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal （Ivr） injections of ranibizumab, with 6 months of follow-up. Retreatment injections were performed based on findings suggestive of active neovascularization. Results： Significant improvements were observed in the juxtafoveal CNV lesions, and average central macular thickness decreased in both groups following the anti-VEGF therapy （P〈0.05）. The average number of injections used in MFC patients was 1.6, while three injections on average were used in wet AMD patients （Z=-2.844, P=0.009）. Best-corrected visual acuity was significantly improved in MFC patients after anti-VEGF therapy （P〈0.05）, and there was no significant difference in wet AMD patients between before anti-VEGF therapy and 6 months later （P〉0.05）. Conclusions： IVT ranibizumab resulted in good clinical outcomes for juxtafoveal CNV secondary to MFC and wet AMD, but the average number of injections used in MFC was fewer than that used in wet AMD over a 6-month observation period. Compared with the wet AMD group, visual acuity was obviously improved in the MFC group at 6 months.

Automatic fovea detection and choroid segmentation for choroidal thickness assessment in optical coherence tomography

AIM:To develop an automated model for subfoveal choroidal thickness(SFCT)detection in optical coherence tomography(OCT)images,addressing manual fovea location and choroidal contour challenges.METHODS:Two procedures were proposed:defining the fovea and segmenting the choroid.Fovea localization from B-scan OCT image sequence with three-dimensional reconstruction(LocBscan-3D)predicted fovea location using central foveal depression features,and fovea localization from two-dimensional en-face OCT(LocEN-2D)used a mask region-based convolutional neural network(Mask R-CNN)model for optic disc detection,and determined the fovea location based on optic disc relative position.Choroid segmentation also employed Mask R-CNN.RESULTS:For 53 eyes in 28 healthy subjects,LocBscan-3D’s mean difference between manual and predicted fovea locations was 170.0μm,LocEN-2D yielded 675.9μm.LocEN-2D performed better in non-high myopia group(P=0.02).SFCT measurements from Mask R-CNN aligned with manual values.CONCLUSION:Our models accurately predict SFCT in OCT images.LocBscan-3D excels in precise fovea localization even with high myopia.LocEN-2D shows high detection rates but lower accuracy especially in the high myopia group.Combining both models offers a robust SFCT assessment approach,promising efficiency and accuracy for large-scale studies and clinical use.

Exogenous testosterone therapy on choroid in androgen deficiency

AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo.

Role of microglial polarization in age-related macular degeneration

Microglia,originating from primitive macrophages in the yolk sac,serves as both immune system defenders and regulators of homeostasis.These cells exhibit two primary polarization states:conventionally activated(M1)and alternatively activated(M2).The polarization of microglia plays a crucial role in influencing inflammatory disorders,metabolic imbalances,and neural degeneration.This process is implicated in various aspects of ocular diseases,especially age-related macular degeneration(AMD),including inflammation,oxidative stress and pathological angiogenesis.The distinct functional phenotypes of microglia impact disease progression and prognosis.Thus,regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches.This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions,emphasizing its relevance in AMD.The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD.

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.

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

Dear Editor,We have read with interest the article by Li et al[1].In the response to this article[1]which is a well thought out and written paper,I would like to draw attention to some critical points in this study and add some comments to the results and the conclusion of the study which authors have detected.In the Li et al’s[1]study,it is detected that,choroidal thickness is significantly negatively correlated with body mass index(BMI)and choroidal thickness is decreased in people with overweight or obesity.

Beta-alanine promotes angiogenesis in laser-induced choroidal neovascularization mice models

AIM:To investigate the effect ofβ-alanine(BA)on laserinduced choroidal neovascularization(CNV)mice models.METHODS:Laser-induced CNV mice models were established,and BA was administrated for one week and two weeks in advance,separately.Furthermore,retinal pigment epithelium(RPE)-choroid flat mounts were separated,and immunohistochemical staining was performed.The laser-induced CNV lesion areas were measured and compared.In addition,liver and kidney morphologies were observed to identify potential hepatorenal toxicity.RESULTS:Enlarged CNV lesion areas were observed in the BA treated group.No significant differences were observed in the liver and kidney sections between groups.CONCLUSION:BA treatment increase CNV lesion areas,suggesting the detrimental effects of BA as a nutritional supplement in age-related macular degeneration(AMD)population.

Automated evaluation of parapapillary choroidal microvasculature in crowded optic discs:a controlled,optical coherence tomography angiography study

AIM:To compare superficial and deep vascular properties of optic discs between crowded discs and controls using optical coherence tomography angiography(OCT-A).METHODS:Thirty patients with crowded discs,and 47 control subjects were enrolled in the study.One eye of each individual was included and OCT-A scans of optic discs were obtained in a 4.5×4.5 mm^(2) rectangular area.Radial peripapillary capillary(RPC)density,peripapillary retinal nerve fiber layer(pRNFL)thickness,cup volume,rim area,disc area,cup-to-disc(c/d)area ratio,and vertical c/d ratio were obtained automatically using device software.Automated parapapillary choroidal microvasculature(PPCMv)density was calculated using MATLAB software.When the vertical c/d ratio of the optic disc was absent or small cup,it was considered as a crowded disc.RESULTS:The mean signal strength index of OCT-A images was similar between the crowded discs and control eyes(P=0.740).There was no difference in pRNFL between the two groups(P=0.102).There were no differences in RPC density in whole image(P=0.826)and peripapillary region(P=0.923),but inside disc RPC density was higher in crowded optic discs(P=0.003).The PPCMv density in the inner-hemisuperior region was also lower in crowded discs(P=0.026).The pRNFL thickness was positively correlated with peripapillary RPC density(r=0.498,P<0.001).The inside disc RPC density was negatively correlated with c/d area ratio(r=-0.341,P=0.002).CONCLUSION:The higher inside disc RPC density and lower inner-hemisuperior PPCMv density are found in eyes with crowded optic discs.

Detecting early changes in choroidal vascularity and thickness using optical coherence tomography in patients with corneal crosslinking for keratoconus

AIM:To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking.METHODS:This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal crosslinking.The choroidal thicknesses were evaluated on enhanced depth imaging optical coherence tomography at the preoperative and postoperative 3d,1,and 3mo.Choroidal thickness in the four cardinal quadrants and the fovea were evaluated.The choroidal vascularity index was also calculated.RESULTS:There was no significant difference in central choroidal thickness between the preoperative and postoperative 3d,1mo(P>0.05).There was a significant increase in the 3mo(P=0.034)and a significant decrease in the horizontal choroidal vascularity index on the postoperative 3d(P=0.014),there was no statistically significant change in vertical axes and other visits in horizontal sections(P>0.05).CONCLUSION:This study sheds light on choroidal changes in postoperative corneal crosslinking for keratoconus.While it suggests the procedure’s relative safety for submacular choroid,more extensive research is necessary to confirm these findings and their clinical significance.

Subretinal fibrosis secondary to neovascular age-related macular degeneration:mechanisms and potential therapeutic targets

Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).