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).

Efficacy comparison of multipoint and single point scanning panretinal laser photocoagulation in non-proliferative diabetic retinopathy treatment

BACKGROUND Non-proliferative diabetic retinopathy(NPDR)poses a significant challenge in diabetes management due to its microvascular changes in the retina.Laser photocoagulation,a conventional therapy,aims to mitigate the risk of progressing to proliferative diabetic retinopathy(PDR).AIM To compare the efficacy and safety of multi-spot vs single-spot scanning panretinal laser photocoagulation in NPDR patients.METHODS Forty-nine NPDR patients(86 eyes)treated between September 2020 and July 2022 were included.They were randomly allocated into single-spot(n=23,40 eyes)and multi-spot(n=26,46 eyes)groups.Treatment outcomes,including bestcorrected visual acuity(BCVA),central macular thickness(CMT),and mean threshold sensitivity,were assessed at predetermined intervals over 12 months.Adverse reactions were also recorded.RESULTS Energy levels did not significantly differ between groups(P>0.05),but the multi-spot group exhibited lower energy density(P<0.05).BCVA and CMT improvements were noted in the multi-spot group at one-month posttreatment(P<0.05).Adverse reaction incidence was similar between groups(P>0.05).CONCLUSION While energy intensity and safety were comparable between modalities,multi-spot scanning demonstrated lower energy density and showed superior short-term improvements in BCVA and CMT for NPDR patients,with reduced laser-induced damage.

Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines

BACKGROUND The prevalence of diabetes mellitus(DM)in China is high,and the base is broad.Diabetic retinopathy(DR)is a critical condition affecting the life and health of a nation and its economic development.DR is a common complication of DM.AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema.METHODS Overall,130 patients with diabetic macular edema(DME)hospitalized in The Third People’s Hospital of Changzhou from January 2019 to June 2022 were retrospectively included.According to the treatment plan,130 patients with DME were categorized into an observation and a control group,with 65 patients in each group.The control group received laser photocoagulation,and the observation group received laser photocoagulation with intravitreal injection of conbercept.Observe changes in vision,cytokines in the eye and so on.RESULTS The total efficacy rate in the observation group(93.85%)was higher than that in the control group(78.46%)(P<0.05).In both groups,the best corrected visual acuity correction effect improved after treatment,and the observation group was superior to the control group(P<0.05).Retinal thickness and central macular thickness improved after treatment,and the observation group was superior to the control group(P<0.05).The levels of vascular endothelial growth factor,interleukin-6,soluble intercellular adhesion molecule-1,and basic fibroblast growth factor in both groups improved after treatment,and the observation group was superior to the control group(P<0.05).CONCLUSION In patients with macular edema,combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision,and lower intraocular cytokine levels.

Retinal laser photocoagulation and intravitreal injection of anti-VEGF for hemorrhagic retinal arterial microaneurysm

AIM:To evaluate the efficacy of retinal laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor(anti-VEGF)for hemorrhagic retinal arterial macroaneurysm(RAM).METHODS:This was a retrospective clinical study.Patients with hemorrhagic RAM were divided into 4 groups defined by different treatments:a retinal laser photocoagulation therapy monotherapy group,an anti-VEGF intravitreal injection monotherapy group,a laser and anti-VEGF combination therapy group,and an observation group.Visual acuity(VA),central macular thickness(CMT),and retinal hemorrhage area(RHA)were collected.RESULTS:Forty-seven eyes of 47 patients were enrolled.VA improved and had a significant difference between baseline and final in each treatment group(logMAR;laser group:1.90±0.53 vs 1.05±0.63,P<0.001;anti-VEGF group:1.75±0.63 vs 1.12±0.54,P=0.009;combination group:1.76±0.38 vs 1.01±0.52,P<0.001);however,VA decreased and had no significant difference in observation group(1.63±0.51 vs 1.76±0.61,P=0.660).CMT decreased and had a significant difference between baseline and final in each group(laser group:815.16±310.83 vs 252.05±83.90μm,P<0.001;anti-VEGF group:725.00±290.79 vs 203.56±69.89μm,P=0.001;combination group:595.50±186.51 vs 253.13±55.06μm,P=0.001;observation group:758.88±195.65 vs 267.00±120.90μm,P=0.001).RHA were 28.99±28.15,25.94±11.58,19.64±8.97,and 27.45±13.76 mm^(2) in laser group,anti-VEGF group,combination group and observation group,respectively.RHA was statistically correlated with final VA(P=0.032)in the observation group.CONCLUSION:Both laser and anti-VEGF treatments are effective for hemorrhagic RAM.Combination therapy reduces the number of injections of anti-VEGF.RHA is a visual prognosis predictor in the natural history of hemorrhagic RAM.

Effects of laser photocoagulation on serum angiopoietin-1, angiopoietin-2, angiopoietin-1/angiopoietin-2 ratio, and soluble angiopoietin receptor Tie-2 levels in type 2 diabetic patients with proliferative diabetic retinopathy

·AIM: To determine the effects of laser photocoagulation on serum levels of angiopoietin-1(Ang-1),angiopoietin-2(Ang-2), soluble angiopoietin receptor Tie-2(Tie-2), Ang-1/Ang-2 ratio and vascular endothelial growth factor(VEGF) in patients with type 2diabetes mellitus(T2DM) and proliferative diabetic retinopathy(PDR). We also explored the role of the Ang/Tie system in PDR.·METHODS:Totally 160patientswithT2 DM, including50 patients with non-diabetic retinopathy(NDR), 58 patients with non-proliferative diabetic retinopathy(NPDR), and52 patients with PDR were enrolled in this study. Serum Ang-1, Ang-2, Tie-2 receptor and VEGF levels were measured using enzyme-linked immunosorbent assays for all patients and were repeated in 26 patients who underwent laser photocoagulation two months after the procedure.·RESULTS:ThemedianlevelsofAng-2andVEGFinserum were significantly higher in the NPDR group(4.23 ng/mL and 303.2 pg/mL, respectively) compared to the NDR group(2.67 ng/mL and 159.8 pg/mL, respectively, P 【0.01), with the highest level in the PDR group(6.26 ng/mL and531.2 pg/mL, respectively, P 【0.01). The median level of Ang-1 was significantly higher in the NPDR group(10.77ng/mL) compared to the NDR group(9.31 ng/mL) and the PDR groups(9.54 ng/mL)(P 【0.05), while no difference was observed between the PDR and NDR groups. Ang-1/Ang-2 ratio of PDR group was lowest in three groups(1.49 vs 2.69 and 2.90, both P 【0.01). The median level of Tie-2was not significantly different among three groups(P 】0.05).Ang-2 was positively correlated with VEGF and Tie-2 in the PDR and NPDR groups(both P 【0.05). Among the 26 patients who underwent laser photocoagulation, serum Ang-2 and VEGF levels significantly decreased(both P 【0.05), whereas serum Ang-1 level and Ang-1/Ang-2ratio were weakly increased(P 】0.05). The median levels of Ang-2 and VEGF in serum were highest in PDR group,however, Ang-1/Ang-2 ratio of PDR group was lowest in three groups.·CONCLUSION: Laser photocoagulation can reduce serum Ang-2 and VEGF levels. The Ang/Tie system and VEGF play an important role in the development and progression of T2 DM patients with PDR.

Is laser photocoagulation still effective in diabetic macular edema? Assessment with optical coherence tomography in Nepal

AIM: To find out the outcome of laser photocoagulation in clinically significant macular edema (CSME) by optical coherence tomography (OCT). · METHODS: It was a prospective, non-controlled, case series study enrolling 81 eyes of 64 patients with CSME between August 2008 and January 2010. All patients received modified grid photocoagulation with frequency doubled Nd: YAG laser. Each patient was evaluated in terms of best-corrected visual acuity (BCVA) and regression or progression of maculopathy after laser therapy at 1, 3 and 6 months. Spearman’s correlation test was used to show the correlation between BCVA and total macular volume (TMV). Analysis of variance (ANOVA) was used to compare among groups and independent t-test was used to compare in each group. · RESULTS: There is high correlation between BCVA and TMV (P ≤0.001). BCVA improved in 50.6%, remained static in 39.5 % and deteriorated in 9.9% patients after 6 month of treatment. The Baseline TMV (mean and SD) were 9.26±1.83, 10.4±2.38, 11.5±3.05, 8.89±0.75 and 9.47±1.98 mm3 for different OCT patterns, ST (sponge like thickening), CMO (cystoid macular edema), SFD (subfoveal detachment), VMIA (Vitreo macular interface abnormality) and average TMV respectively (P =0.04). After 6 months of laser treatment, the mean TMV decreased from 9.47±1.98mm3 to 8.77±1.31mm3(P =0.01). In ST there was significant decrease in TMV, P =0.01, Further within these groups at 6 months, they were significantly different, P =0.01. · CONCLUSION: OCT showed the different morphological variant of CSME while the response of treatment is different. TMV decreased the most and hence showed the improvement in vision after 6 months of laser treatment. In the era of Anti vascular endothelial growth factors (VEGFs), efficacy of laser seems to be in shadow but it is still first line of treatment in developing nation like Nepal where antiVEGFs may not be easily available and affordable.

Short-term effects of intravitreal Conbercept injection combined with laser photocoagulation on macular edema secondary to ischemic retinal vein occlusion

AIM:To observe changes in the best-corrected visual acuity(BCVA),central macular thickness(CMT),and central choroidal thickness(CCT)of patients with macular edema(ME)secondary to ischemic retinal vein occlusion(i RVO)following intravitreal Conbercept injection.METHODS:This retrospective study included 33 eyes from 33 patients who received intravitreal injections of Conbercept for ME secondary to i RVO.Treatments were performed on a 3+pro re nata(3+PRN)basis.All of the patients were examined by fundus fluorescein angiography and spectral domain optical coherence tomography at the first visit.Laser photocoagulation was performed in the nonperfusion area of the retina of all eyes after the first injection.BCVA,CMT,and CCT were observed before and after 6 mo of treatment.The number of injections necessary to achieve improved vision was also noted.RESULTS:Following Conbercept treatment,the mean BCVA significantly improved from 0.81±0.39 at baseline to 0.41±0.25 and 0.43±0.29 log MAR in the third and sixth months,respectively(both P=0.000).The CMT of the patients at baseline was 556.75±98.57μm;304.78±68.53 and 306.85±76.77μm 3 and 6 mo after treatment,respectively(both P=0.000 vs baseline).The CCTs of the patients at baseline,3 and 6 mo after treatment were 304.63±57.83,271.31±45.53,and 272.29±39.93μm,respectively(P=0.026 and 0.035 vs baseline).No severe adverse event relevant to the therapy was noted,and the average number of injections delivered was 3.35.CONCLUSION:Intravitreal Conbercept injection combined with laser photocoagulation appears to be a safe and effective treatment for ME secondary to i RVO in the short-term.

Effects of diode laser photocoagulation treatment on ocular biometric parameters in premature infants with retinopathy of prematurity

AIM:To investigate the effects of diode laser treatment on ocular biometric parameters in premature infants with retinopathy of prematurity(ROP).METHODS:Premature infants who received diode laser treatment for ROP(n=68)and premature infants with spontaneous regressed ROP without treatment(n=50)were performed longitudinal ocular biometric measurements including anterior chamber depth,lens thickness and axial length as follows:1 d prior to laser treatment,and 3,6,9,and 12 mo after the laser treatment.RESULTS:The mean birth weight,gestational age and initial examination time values were 936.53±302.07 g,26.66±2.42 wk,36.26±2.73 wk in the treatment group and 959.78±260.08 g,27.28±2.10 wk,36.56±2.54 wk in the control group.There was no statistically significant difference in these demographic characteristics of the groups.Anterior chamber depth,lens thickness and axial length demonstrated statistically significant linear increases during the study period in the two groups(P<0.001 for each).There were no statistically significant differences between the two groups in terms of anterior chamber depth after laser treatment.Measurements of the lens thickness at 9 th and 12 th months(9 th month 3.70±0.22 vs 3.60±0.21 mm,P=0.017;12 th month 3.81±0.21 vs 3.69±0.22 mm,P=0.002)and the axial length at 12 th month(19.35±0.79 vs 19.13±0.54 mm,P=0.031)after laser treatment were statistically higher in the treatment group.CONCLUSION:Diode laser retinal photocoagulation treatment in premature infants seems to increase the lens thickness and axial length.

Prophylactic juxtapapillary laser photocoagulation in pediatric morning glory syndrome

AIM:To determine the anatomic and visual outcomes of prophylactic juxtapapillary laser photocoagulation treatment alone in the prevention of retinal detachment(RD)in a cohort of pediatric patients diagnosed with morning glory syndrome(MGS).METHODS:A total of 24 eyes of 22 consecutive patients aged 0-15 y diagnosed with MGS treated with prophylactic juxtapapillary laser photocoagulation alone were reviewed.Data including demographics,ocular examination,anatomic and visual outcomes,following treatment and complications were collected.RESULTS:Two patients had bilateral laser treatment and 20 had monocular laser treatment.The age at treatment of 13(59.1%)patients was less than 12 mo.The presenting symptoms included strabismus(6/22,27.3%),decreased vision(2/22,9.1%),and routine fundus screening(14/22,63.6%).Fifteen(68.2%)patients underwent cranial magnetic resonance imaging(MRI)examinations,and 3 of those 15(20.0%)had abnormal findings in the nervous system.Based on preoperative wide-field fundus photography and B-scan echography,all(100.0%)eyes had no obvious RD.On postoperative 1 mo and 6 mo and the following follow-ups,the anatomic outcomes of all eyes remained stable.The mean follow-up duration was 27.7±17.5 mo.No severe complications were found.Preoperative visual acuity acquired from 2(9.1%)patients ranged from light perception to 20/200.Postoperative acuity acquired from 11(50.0%)patients ranged from light perception to 20/125.CONCLUSION:The preliminary anatomic and visual outcomes of prophylactic juxtapapillary laser treatment alone in pediatric MGS patients are relatively stable in a short-term follow-up.Further long-term clinical observation will be needed to confirm its efficacy and safety.

Dan Huang Ming Mu Recipe Suppresses the Progression of Streptozotocin-induced Diabetic Retinopathy After Retinal Laser Photocoagulation in Brown Norway Rats via Down-regulating Vascular Endothelial Growth Factor and Up-regulating Pigment Epithelium-derived

Objective To analyze the effects of Dan Huang Ming Mu Recipe(DHMMR)(a pharmaceutical preparation from herbs and having the function of replenishing vital essence,removing heat,promoting blood circulation and excreting pathogenic water) on diabetic retinopathy(DR) after retinal laser photocoagulation through regulating the expression of vascular endothelial growth factor(VEGF) and pigment epithelium-derived factor(PEDF).Methods Forty male Brown Norway(BN) rats were randomly divided into blank group(group A,10 BN rats) and model group(30 BN rats).DR models were induced by 40 mg/kg streptozotocin(STZ) and the body weight and blood glucose of rats were monitored.After 12-week injection,fluorescein fundus angiography(FFA) and histopathological examination were detected to confirm the successful establishment of DR models.Subsequently,the right eyes of model group rats were conducted retinal laser photocoagulation with the left eyes having no retinal laser photocoagulation and rats of the model group were randomly divided into group B(the model control group),group C(the positive control group),and group D(the DHMMR group),with 10 rats in each group.Rats of the group A and the group B were given vehicle,and the group C were given calcium dobesilate suspension by gavage,and the group D were given DHMMR by gavage.After 4-week gavage,FFA was carried out to observe the fundus microvascular change.Then,the rats were sacrificed to do histopathological examinations and the serum levels of P-selectin,cAMP,cGMP,and the relative expression of the protein of VEGF and PEDF in retina were detected.Results After 12-week STZ injection,the blood glucose of the model group were pronouncedly higher than the blank group(P < 0.01).Fundus micro-hemangioma changes were observed in the rats of the model group through FFA,and the rats of the blank group did not see any changes.The pictures of HE staining showed that the retinal structure of the model group was more disordered than the blank group.After 4-week gavage,treatments with DHMMR showed dramatic reduction of serum levels of Pselectin,cAMP and cGMP compared with the group B(P < 0.01).FFA and histopathological examinations of DHMMR-treated rats revealed significantly suppression of retinal edema,fundus microvascular destruction and retinal destruction distinguishing from the group B.And the relative expression of VEGF protein of the group D and the group A was markedly lower than that of the group B(P < 0.01).The relative expression of PEDF protein of the group D and the group A was dramatically higher than that of the group B to the contrary(P < 0.01).Conclusions DHMMR demonstrates pronounced suppressive effects on the progression of DR after retinal laser photocoagulation,through down-regulating VEGF and upregulating PEDF.

Long-term outcomes of focal laser photocoagulation for the treatment of polypoidal choroidal vasculopathy

AIM:To evaluate the long-term effect and safety of focal laser photocoagulation treatment in eyes with polypoidal choroidal vasculopathy(PCV).METHODS:Medical records of 13 eyes of 13 patients with PCV were followed-up for more than 2 y after focal laser photocoagulation treatment.The patients were diagnosed with PCV using indocyanine green angiography,and eyes with other comorbid ocular diseases were excluded.The measurement outcomes of the study were the post-treatment regression and recurrence of polyps,complications,and changes in visual acuities.Paired t-test was performed to compare visual outcome before and after the treatment.RESULTS:The mean age of the 13 patients was 70.2±5.5 y,and the follow-up period was 72.3±31.0(range,25-118)mo.Three eyes had juxtafoveal polyps and 10 eyes had extrafoveal polyps.Of the 13 eyes,9 eyes(69.2%)had regression of polyps 1.7±1.2(range,0.9-4)mo after focal laser photocoagulation.Five eyes(55.6%)showed recurrence of polyps during the follow-up periods,and the recurrence period was 12.8±18.9(range,1.9-48)mo.Mild subretinal hemorrhage occurred in two eyes(15.4%)27 and 72 d after laser treatment,respectively.There were no statistically significant differences in visual acuities at baseline;1,2,3 y post-treatment(all P>0.05);and last follow-up(0.63±0.5,0.73±0.70,0.67±0.57,0.75±0.7,and 0.95±0.8 log MAR,respectively).CONCLUSION:Focal laser photocoagulation is beneficial for early regression of polyps in eyes with PCV and does not result in significant submacular hemorrhage during the long-term follow-up.Furthermore,it can be primarily considered in eyes with PCV with extrafoveal or juxtafoveal polyps to regress risky polyps as well as to maintain visual acuity without serious hemorrhagic complications.

Effect of two different doses of intravitreal bevacizumab with temporal retina-sparing laser photocoagulation for retinopathy of prematurity

This study aims to compare the efficacy and safety between two different doses of intravitreal bevacizumab（IVB） injection with temporal retina-sparing laser（TRSL） photocoagulation for retinopathy of prematurity（ROP）. We retrospectively evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for stage 3＋ zone I or posterior zone II ROP. Laser photocoagulation was applied on the avascular retina, sparing two-discdiameter width temporal avascular area anterior to ridge. A half dose（0.625 mg） or minimal dose（0.25 mg） of IVB was conducted. Four eyes in minimal dose group were retreated with IVB and laser photocoagulation on the spared retina. Of those 4 retreated eyes, three developed preretinal hemorrhage around the ridge after the first treatment, resulting in fibrotic macular dragging. A half dose of IVB may be more effective than a minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger of poor prognosis.

Short-term effectiveness of intelligent navigated laser photocoagulation versus subthreshold micropulse laser in patients with chronic central serous chorioretinopathy

AIM:To compare the short-term effectiveness of intelligent navigated laser photocoagulation and 577-nm subthreshold micropulse laser(SML)treatment in patients with chronic central serous chorioretinopathy(cCSC).METHODS:This observational retrospective cohort study included 60 consecutive patients who underwent intelligent navigated laser photocoagulation(n=30)or 577-nm SML treatment(n=30)for cCSC between Jan.2021 and Oct.2022.During 3mo follow-up,all patients underwent assessments of best correct visual acuity(BCVA)and optical coherence tomography(OCT).RESULTS:The operation of laser treatment was successful in all cases.At 1mo,BCVA improved significantly more in the intelligent navigated laser photocoagulation group compared to the SML group(P<0.05).The change was not significantly different at 3mo(P>0.05).Central macular thickness(CMT)in the intelligent navigated laser photocoagulation group was lower than in the SML group at 1mo(P<0.05).The subfoveal choroidal thickness(SFCT)in two groups were all significantly improved at 3mo(all P<0.05).The change between two groups was not significantly different at 1mo or at 3mo(P>0.05).CONCLUSION:Intelligent navigated laser photocoagulation is superior to SML for treating cCSC,leading to better improvements in vision and CMT for short term.

A COMPARATIVE STUDY ON CELLULAR ELECTROPHYSIOLOGIC CHANGES BETWEEN LASER PHOTOCOAGULATION AND RADIOFREQUENCY ABLATION

In order to investigate the differences of cellular electrophysiologic changes between laser photocoagulation(LP) and radiofrequency ablation(RFA), transmembrane potentials were recorded at 0 5,1,3,5,8 mm from lesions before and after LP and RFA had been performed respectively on 15 endocardial tissues removed from 15 adult rabbits in each group Resting potential(RP), action potential amplitude(APA), maximum rate of upstroke velocity (dV/dT), and action potential duration at 50 percent of repolarization(APD50) decreased at 0 5, 1,3 mm from lesions in RF, so did all of them at 0 5,1 mm in LP, but all transmembrane potential variables were almost normal at 3 mm in LP Furthermore, almost all the transmembrane potential variables at 0 5 1,3 mm in RFA went down much lower than those in LP(P<0 01) There was no difference in all transmembrane potential variables at 5, 8 mm between LP and RFA APD 90 had no difference at varing distance in both the groups Electrophysiologic abnormalities of border zone of injured but nonnecrotic myocardium around the lesions of laser photocoagulation are much less than those of radiofrequency ablation in strength and much smaller in scope, which suggest that unfavorable effects of laser photocoagulation on hemodynamics and arrhythmogenicity would be less than those of radiofrequency ablation

Progress in the Treatment of DME

Diabetic macular edema (DME) is a common ocular complication of diabetes mellitus (DM) and an important cause of vision loss. The pathogenesis of DME is complex and can occur at any time of diabetic retinopathy (DR). Effective methods of treating DME are essential to prevent irreversible damage to visual function. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated their therapeutic efficacy in large randomized controlled trials and real-life observational studies. Clinicians need to consider various factors, such as efficacy, safety, accessibility, and cost, in the selection of various options. This review summarizes the current therapeutic approaches for DME to provide new references for the treatment of DM.

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the eye.Diabetic retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to blindness.Several epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and ethnicity.Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia.The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging.This review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

Comparison of anti-vascular endothelial growth factors, laser treatments and a combination of the both for treatment of central retinal vein occlusion

AIM：To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion（CRVO）treated with intravitreal injections of bevacizumab,macular grid photocoagulation combined with pan retinal photocoagulation（PRP）,or both（bevacizumab＋grid＋PRP）.· METHODS：Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema.Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12 mo after treatment.Excluded were patients with diabetes or any other retinal disease.We reviewed the medical records of patients treated in one ophthalmology departmentcomparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both.The main outcome measures were the differences in best corrected visual acuity（BCVA） and in macular thickness,as assessed by optical coherence tomography,between the enrollment and the final follow up visits.· RESULTS：Sixty-five patients met inclusion criteria.There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography（131.5±41.2,108.6±29.2,and 121.1±121.1,P=0.110）,or in visual acuity（0.128±0.077,0.088±0.057,and 0.095±0.065）,for intravitreal injections,macular grid photocoagulation＋PRP and a combination of the treatments,respectively,P =0.111.The proportions of patients with macular edema after treatment were：26.1%,28.6%,and 14.3%,respectively,P=0.499.· CONCLUSION：Similar benefit was observed for intravitreal injections,laser photocoagulation,or a combined regimen in the treatment of CRVO.A nonstatistically significant trend for reduction in macular edema was observed following combined treatment.

Foveal structure changes in infants treated with anti-VEGF therapy or laser therapy guided by optical coherence tomography angiography for retinopathy of prematurity

AIM: To evaluate foveal vessel density(VD) and foveal thickness using optical coherence tomography angiography(OCTA) in retinopathy of prematurity(ROP) children treated with laser photocoagulation or anti-vascular endothelial growth factor(VEGF) injection. Additionally, we assessed the relationship between foveal microvascular anomalies and different therapies in ROP children.METHODS: This was a single-center, retrospective study of patients with a diagnosis of type 1 ROP. Twenty-three eyes(14 patients) treated with anti-VEGF injection and twentynine eyes(17 patients) treated with laser coagulation were included in this study. The foveal VD, inner thickness and full thickness were measured at the central 0°, 2° to 8°, and 8° of the retina(centered on the fovea) using OCTA and cross-sectional OCT, respectively.RESULTS: Foveal VD, inner thickness and full thickness were significantly smaller within the central 8° of the retina in ROP children treated with anti-VEGF injection than in those treated with laser photocoagulation(P=0.013, 0.009, 0.036, respectively). The full thickness was also smaller in the anti-VEGF group than in the laser group at the central 0° of the retina(P=0.010). The grade of foveal hypoplasia is lower in the anti-VEGF group than in the laser group(P=0.045). Multivariable analysis did not find any risk factors associated with visual acuity in our study.CONCLUSION: In children with type 1 ROP, the better structural development of fovea in those who were treated with anti-VEGF injection compared with laser photocoagulation are identified. However, visual acuity outcomes are similar 70 mo after the treatments.

Sub-threshold micro-pulse diode laser treatment in diabetic macular edema： a Meta-analysis of randomized controlled trials

AIM：To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation（SDM） and traditional modified Early Treatment Diabetic Retinopathy Study（mETDRS）treatment protocol in diabetic macuiar edema（DME）.METHODS：A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME.The participants were type Ⅰ or type Ⅱ diabetes mellitus with clinically significant macuiar edema treated by SDM from previously reported randomized controlled trials（RCTs）.The primary outcome measures were the changes in the best corrected visual acuity（BCVA） and the central macuiar thickness（CMT） as measured by optical coherence tomography（OCT）.The secondary outcomes were the contrast sensitivity and the damages of the retina.RESULTS：Seven studies were identified and analyzed for comparing SDM（215 eyes） with mETDRS（210 eyes）for DME.There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up：3mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.77）,6mo（MD,-0.02;95% Cl,-0.12 to 0.09;P=0.75）,12mo（MD,-0.05;95% Cl,-0.17 to 0.07;P=0.40）.Likewise,there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo（MD,-9.92;95% Cl,-28.69 to 8.85;P=0.30）,6mo（MD,-11.37;95% Cl,-29.65 to 6.91;P=0.22）,12mo（MD,8.44;95% Cl,-29.89 to 46.77;P=0.67）.Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS,in two different followup evaluations：3mo（MD,0.05;95% Cl,0 to 0.09;P=0.04） and 6mo（MD,0.02;95% Cl,-0.10 to 0.14;P=0.78）.Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did（OR,0.05;95% Cl,0.02 to 0.13;P〈0.01）.CONCLUSION：SDM laser photocoagulation shows an equally good effect on visual acuity,contrast sensitivity,and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.

Protective effect of basic fibroblast growth factor on laser induced retinopathy

AIM:To investigate the side effects of the commonly used laser treatment along with testing the neuroprotective effect of bFGF on a potential retinal impairment.METHODS:To do this,30 chinchilla pigmented adult male rabbits were divided into the control and experimental groups.The control and experimental groups underwent both laser application and bFGF treatment.The retinal tissue impairment and its renewal rate were tested under the light and electron microscopical levels.RESULTS:The focal laser application on rabbit eyes caused morphological alterations both in the application region and in the neighbouring areas.In the damaged areas,the outer nuclear layer of the neural retina was almost disappeared,retina pigment epithelium was interrupted,the retina pigment epithelium migrated intraretinally,and the damaged region along with neighbouring areas seemed to be not separated.bFGF application just after the laser photocoagulation,revealed better results in application areas.CONCLUSION:It could be suggested that the bFGF application following laser photocoagulation might have protective,repairing and wound healing effects on the retina.