Biomaterial engineering strategies for modeling the Bruch's membrane in age-related macular degeneration

Age-related macular degeneration,a multifactorial inflammatory degenerative retinal disease,ranks as the leading cause of blindness in the elderly.Strikingly,there is a scarcity of curative therapies,especially for the atrophic advanced form of age-related macular degeneration,likely due to the lack of models able to fully recapitulate the native structure of the outer blood retinal barrier,the prime to rget tissue of age-related macular degeneration.Standard in vitro systems rely on 2D monocultures unable to adequately reproduce the structure and function of the outer blood retinal barrier,integrated by the dynamic interaction of the retinal pigment epithelium,the Bruch's membrane,and the underlying choriocapillaris.The Bruch's membrane provides structu ral and mechanical support and regulates the molecular trafficking in the outer blood retinal barrier,and therefo re adequate Bruch's membrane-mimics are key for the development of physiologically relevant models of the outer blood retinal barrie r.In the last years,advances in the field of biomaterial engineering have provided novel approaches to mimic the Bruch's membrane from a variety of materials.This review provides a discussion of the integrated properties and function of outer blood retinal barrier components in healt hy and age-related macular degeneration status to understand the requirements to adequately fabricate Bruch's membrane biomimetic systems.Then,we discuss novel materials and techniques to fabricate Bruch's membrane-like scaffolds for age-related macular degeneration in vitro modeling,discussing their advantages and challenges with a special focus on the potential of Bruch's membrane-like mimics based on decellularized tissue.

Effects of vitrectomy combined with internal limiting membrane peeling in patients with diabetic macular edema

BACKGROUND Diabetic macular edema(DME),a chronic microvascular complication of diabetes,is a leading cause of visual impairment and blindness.Pars plana vitrectomy(PPV)can restore the normal macular structure and reduce macular edema,whereas internal limiting membrane(ILM)peeling is used to treat tractional macular diseases.Despite the advantages,there is limited research on the combined effects of PPV with ILM peeling.AIM To observe the effects of PPV combined with ILM peeling on postoperative central macular thickness(CMT),best-corrected visual acuity(BCVA),cystoid macular edema(CME)volume,and complications in patients with DME.METHODS Eighty-one patients(92 eyes)diagnosed with DME at the Beijing Shanqu Liangxiang Hospital between January and December 2022 were randomly divided to undergo PPV alone(control group:41 patients,47 eyes)or PPV+ILM peeling(stripping group:40 patients,45 eyes);a single surgeon performed all surgeries.The two groups were compared preoperatively and 1 and 3 months postoperatively.RESULTS Preoperatively,both groups had comparable values of CMT,BCVA,and CME volume(P>0.05).After surgery(both 1 and 3 months),both groups showed significant reductions in CMT,BCVA,and CME volume compared to preoperative levels,with the stripping group showing more significant reductions compared to the control group(P<0.05).Further repeated-measures ANOVA analysis for within-group differences revealed significant effects of group and time,and interaction effects for CMT,BCVA,and CME volume(P<0.05).There were no significant differences in the incidence of complications between the groups(retinal detachment:control=2,stripping=1;endophthalmitis:Control=4,stripping=1;no cases of secondary glaucoma or macular holes;χ^(2)=0.296,P=0.587).CONCLUSION PPV with ILM peeling can significantly improve the visual acuity of patients with DME,reduce CMT,and improve CME with fewer complications.

Inverted internal limiting membrane flap technique for very large macular hole

AIMTo assess the anatomical and visual outcome of idiopathic macular holes greater than 1000 &#x000b5;m using the inverted internal limiting membrane flap technique.METHODSThis retrospective case series included 5 eyes of 5 patients with idiopathic macular hole with base diameter greater than 1000 &#x000b5;m who underwent inverted internal limiting membrane flap technique along with standard 23G pars plans vitrectomy with posterior hyaloid detachment and fluid gas exchange with 12%-14% perfluoropropane (C3F8). Preoperative and postoperative visual acuity and spectral domain optical coherence tomography images were evaluated. The main outcome measures were visual outcome and macular hole closure.RESULTSMean age was 63.2&#x000b1;8.4y with all 5 subjects being females. Mean duration of symptoms was 11&#x000b1;14mo with a mean postoperative follow up of 13.2&#x000b1;13mo. The mean base diameter of the macular holes was 1420&#x000b1;84.8 &#x000b5;m (1280-1480 &#x000b5;m). Type 1 closure was achieved in four out of five patients, while one patient had type 2 closure using the inverted internal limiting membrane (ILM) flap technique. Median baseline BCVA was 0.79 logMAR (Snellen’s equivalent 20/120) and median final BCVA 0.6 logMAR (Snellen’s equivalent 20/80) with mean visual improvement of approximately three lines improvement. No complications related to surgical procedure were noted.CONCLUSIONThe inverted internal limiting membrane flap technique may be promising for very large macular holes with high rate of macular closure and good visual outcome.

Treatment of refractory giant macular hole by vitrectomy with internal limiting membrane transplantation and autologous blood

AIM：To investigate the effect of internal limiting membrane transplantation and autologous blood on treating refractory giant macular hole.METHODS：Thirty-seven eyes with giant macular hole of the smallest hole diameter 〉700 μm,the maximum diameter of the substrate 〉1000 μm and hole formation factor 〈0.6 underwent surgical treatment.The patients were randomly divided into two groups.Nineteen eyes with surgical flip of the internal limiting membrane in group A,18 eyes with internal limiting membrane transplantation in group B who underwent the tamponade of internal limiting membrane into the hole,autologous plasma was used to seal the hole.The patients were followed up for 3 mo,optical coherence tomography and best corrected visual acuity（BCVA） were recorded before and after operation,and the results were statistically analyzed.RESULTS：At 3 mo after operation,BCVA of the two groups was significantly improved compared with that before operation（tA=4.192,tB=4.374,P〈0.05）.But there was no significant difference in visual acuity between the two groups（χ^2=0.128,P〉0.05）.At 3 mo after operation,the closure rate of group A was 68.4%,and 100% in group B.（χ^2=5.628,P〈0.05）.The defect diameter of inner segment/outer segment at 3 mo after the operation was significantly lower than that before operation（tA=12.287,tB=15.481,P〈0.05）,and the difference was statistically significant（t=2.552,P〈0.05）.CONCLUSION：Internal limiting membrane transplantation combined with autologous whole blood can improve the postoperative closure rate of the refractory large aperture,and can effectively improve the postoperative visual acuity.

Outcomes of 4 surgical adjuvants used for internal limiting membrane peeling in macular hole surgery: a systematic review and network Meta-analysis

AIM:To compare the outcomes of four adjuvants used for internal limiting membrane(ILM)peeling in macular hole surgery,including indocyanine green(ICG),brilliant blue G(BBG),triamcinolone(TA)and trypan blue(TB),through systematic review and random-effects Bayesian network Meta-analysis.METHODS:PubMed,Cochrane library databases and Web of Science were searched until August 2018 for clinical trials comparing the above four adjuvants.ORs for postoperative best corrected visual acuity(BCVA)improvement and primary macular hole closure rates were compared between the different adjuvants.RESULTS:Twenty-seven eligible articles were included.For postoperative BCVA improvement,results of BBGassisted peeling were significantly more favorable than those of ICG(WMD 0.08,95%credible interval 0.01-0.16)and TA ranked highest.No significant differences were found between any other two groups in postoperative BCVA improvement.For postoperative primary macular hole closure rates,BBG ranked highest.However,no significant differences were shown between any two groups.CONCLUSION:TA and BBG are the optimum adjuvants for achieving postoperative BCVA improvement macular hole surgery with adjuvant-assisted ILM peeling.Among all adjuvants,the use of BBG is associated with the highest postoperative macular hole closure rate.

Efficacy and safety of vitrectomy with internal limiting membrane peeling for diabetic macular edema: a Meta-analysis

AIM： To evaluate the efficacy and safety of vitrectomy with internal limiting membrane（ILM） peeling for diabetic macular edema（DME）. METHODS： The PubMed, Embase, Web of Science, Cochrane, SionMed, ClinicalTrials.gov, CNKI databases and Wanfang databases, published until Oct. 2017, were searched to identify studies comparing the clinical outcomes following vitrectomy with and without ILM peeling, for treating DME. Pooled results were expressed as odds ratios（ORs） with corresponding 95% confidence intervals（CI） for vitrectomy with and without ILM peeling with regard to best corrected visual acuity（BCVA）, central macular thickness（CMT）, and complication incidents. RESULTS： A total of 14 studies involving 857 eyes were included of which three studies were Chinese and the rests were English literatures. Meta-analysis indicated that compared with vitrectomy alone, vitrectomy with ILM peeling could improve BCVA more obviously（OR=1.66, 95%CI： 1.12-2.46, P=0.01） and had higher rate of CMT reduction（OR=3.89, 95%CI： 1.37-11.11, P=0.01）. There were significant statistical differences between the two surgical methods for both BCVA and CMT（P〈0.05）. For the incidence of intraoperative and postoperative complications, the incidence of epiretinal membrane（ERM） was slightly lower in the ILM peeling group than the group without ILM peeling（OR=0.38, 95%CI： 0.07-2.00, P=0.25）, although insignificant statistically. Other incidences of overall complications, iatrogenic peripheral retinal break and increased intraocular pressure indicated no significant difference between two groups（OR=1.19, 95%CI： 0.82-1.73, P=0.36; OR=1.21, 95%CI： 0.66-2.21, P=0.53; OR=1.34, 95%CI： 0.75-2.40, P=0.32）. CONCLUSION： Vitrectomy is effective for DME and the effect can be improved by additional ILM peeling, especially for anatomical efficacy, without increasing the incidence of intraoperative and postoperative complications. However, it is imperative to gain more evaluation in the future due to the paucity of prospective randomized study.

Free autologous internal limiting membrane transplantation in the treatment of large macular hole

We evaluated the clinical efficacy of free internal limiting membrane(ILM) flap transplantation for the treatment of large macular hole over 500 μm in 42 consecutive patients. Quantified evaluation of the post-operative macular anatomy restoration was performed by spectral-domain optical coherence tomography in the 12 mo follow-up. The results showed 41 eyes achieved successful closure(97.6%). Postoperative best corrected visual acuity, ellipsoid layer, and external limiting membrane disruption were significantly improved at all follow-up time points. The central foveal thickness was significantly higher at 1 mo. We concluded that free ILM flap transplantation proves to be effective to achieve anatomical and functional improvement for the treatment of large macular hole.

Internal limiting membrane flap technique in macular hole surgery

Vitrectomy combined with internal limiting membrane(ILM)peeling is popular for the treatment of macular hole(MH).However,the improvements of MH closure rate and postoperative visual acuity are not satisfactory especially in large and refractory MHs.Currently,the ILM flap technique has gradually been applied for the treatment of MH and achieved high MH closure rate.The ILM flap technique has many variations,including the difference of the size,shape,number,and manner in which the flaps put on the MHs.The ILM flap technique also has some auxiliary means including perfluoro-n-octane(PFO),dye,autologous blood and adhesive viscoelastics.There is controversy about the effects between several technique variations of ILM flap,and it needs to be explored in the future.

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection

AIM:To explore the efficacy of minimally invasive vitrectomy(MIV)with or without internal limiting membrane(ILM)peeling on the treatment of diabetic macular edema(DME)in proliferative diabetic retinopathy(PDR)combining with preoperative anti-vascular endothelial growth factor(anti-VEGF)injection.METHODS:Totally 132 eyes(132 patients)diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye Hospital.The single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 eyes.Anti-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to 3y.Best-corrected visual acuity(BCVA),central retinal thickness(CRT),total macular volume(TMV),macular edema(ME)severity,intraocular pressure(IOP),and complications were recorded.Prognostic factors of visual acuity following ILM peeling were analyzed.RESULTS:The BCVA was higher than preoperative values at 1,3,6,and 12mo after surgery in both groups(all P<0.05).At 6 and 12mo,the BCVA of the combined group was significantly higher than that of the MIV only group(0.52±0.23 v/s 0.64±0.29 IogMAR,P=0.011 in 6mo;0.41±0.25\/s 0.52±0.25 IogMAR,P=0.008 in 12mo).Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1^(st) month(lmo 397.65±106.18 vs 451.94±118.88 μm in MIV only group;388.88±108.68 v/s 464.36±111.53 μm in combined group;both P<0.05)and decreased gradually.The differences between the two groups were statistically significant at 3,6,and 12mo(P=0.004,0.003,0.00 respectively).The TMV was decreased from the 3^(rd) month in the single treatment group(3mo 11.14±1.66 vs 12.20±2.09 mm^(3),P<0.05).At 12mo,the proportion of eyes with edema that had CRT more than 350μm was significantly lower than before surgery(13.24%vs 77.94%in MIV only group;1.56%vs 81.25%in combined group;both P<0.05).There was no significant difference in the recurrence incidence of macular epiretinal membrane,ME,transient IOP increase,vitreous rebleeding,or traction retinal detachment between the two groups.BCVA after ILM excision was positively correlated with the CRT and ME degree before and after surgery(r=0.430,0.485,respectively;P<0.05).CONCLUSION:MIV combined with ILM peeling accelerates the absorption of ME,improves vision,reduces the postoperative CRT and TMV,and reduces the recurrence rate of postoperative ME.

Amniotic membrane for covering high myopic macular hole associated with retinal detachment following failed primary surgery

AIM:To evaluate the therapeutic effect of amniotic membrane(AM)for covering high myopic macular hole associated with retinal detachment following failed primary surgery.METHODS:Seventeen eyes of 17 patients whose axial length was more than 29 mm suffered from macular hole(MH)or MH associated with retinal detachment(RD),and had previously surgery of pars plana vitrectomy(PPV)with internal limiting membrane(ILM)peeling and silicone oil(SO)tamponade.Half a year after the surgery,optical coherence tomography(OCT)showed that MH did not heal in all 17 eyes and RD was still maintained in 13 eyes of these 17 eyes.We performed SO removal combined with AM covering on macular area and C3 F8 tamponade,and phacoemulsification combined with intraocular lens implantation simultaneously cataract eyes.We followed up these patients for one year.RESULTS:In all 17 eyes,SO was removed successfully,MHs were healed and RDs were reattached.One eye(5.89%,1/17)had AM shifted half a month after surgery and underwent a second surgery to adjust the position of the AM and supplement C3 F8.After surgery,the visual acuity(VA)improved in 15 eyes(88.24%,15/17),no change in two eyes(11.76%,2/17).No serious complications occurred in all eyes.CONCLUSION:AM covering is helpful to rescue the previous failure surgery of high myopic MH.

Internal limiting membrane peeling with different dyes in the surgery of idiopathic macular hole: a systematic review of literature and network Meta-analysis

AIM: To evaluate the effect of internal limiting membrane(ILM) peeling with indocyanine green(ICG), brilliant blue G(BBG), triamcinolone acetonide(TA), trypan blue(TB), or without dye for the treatment of idiopathic macular hole(IMH). METHODS: A search was conducted using Pub Med, EMBASE, and CENTRAL(Cochrane Central Register of Controlled Trials) for related studies published before October 2018. RESULTS: A total of 29 studies and 2514 eyes were included in this network Meta-analysis. For IMH closure, the rank from the best to the worse treatment was: BBG, TB, TA, ICG, and no dye. There was a significant difference in postoperative IMH closure rate between BBG and no dye. The rank of the best to the worse treatment to improve visual acuity was: BBG, TB, no dye, TA, and ICG. The improvement rate of visual acuity after using BBG was significantly higher than ICG. The improvement rate of visual acuity was more favorable with TB than ICG, TA, and no dye. CONCLUSION: BBG can contribute to better anatomical and functional outcomes compared to other dyes for ILM peeling in patients with IMH. The results show that the best treatment of ILM peeling with dyes is BBG.

Internal limiting membrane dragging and peeling:a modified technique for macular holes closure surgery

AIM:To introduce a modified technique of internal limiting membrane(ILM)centripetal dragging and peeling to treat idiopathic macular hole(IMH)and to observe the ILM-retina adhesive forces.METHODS:Twenty-six consecutive patients with stage 3 to 4 IMH and followed up at least six months were enrolled.All patients underwent complete par plana vitrectomy,ILM dragging and peeling,fluid and gas exchange,15%C3 F8 tamponade and 2-week prone position.The best corrected visual acuity,macular hole evaluation by optical coherence tomography,and complications were evaluated.RESULTS:The mean diameter of IMH was 524±148μm(range:201-683μm),with 21 cases(80.8%)greater than 400μm.ILM dragging and peeling were successfully performed in all cases.Most of the ILM-retina adhesive forces are severe(42.3%,11/26),followed by mild(38.5%,10/26),and moderate(19.2%,5/26).The mean follow-up duration was 21.2±6.1 mo.The IMH was closed in 25(96.3%)eyes.Visual acuity(logMAR)improved significantly from 1.2±0.6 preoperatively to 0.7±0.5 postoperatively(P<0.001).CONCLUSION:Preexisting ILM-retina adhesive force is found in IMH patients.With assistance of this force,this modified technique may help to release the IMH edges and improve the closure rate of large IMH.

The impact of macular surgery in different grades of epiretinal membrane

AIM：To assess the impact of macular surgery on the functional and anatomic outcomes of the patients in different grades of epiretinal membrane（ERM）.METHODS：Seventy-one eyes of 71 patients who underwent 23-gauge transconjunctival sutureless pars plana vitrectomy for primary isolated ERM were evaluated in this study.RESULTS：There were 38 females（53.5%） and 33 males（46.5%）.The average age of the patients was 68.1 y（range 42-89 y）.Mean follow up period was 14 mo（range 6-26 mo）.The cases were divided into two subgroups of cellophane maculopathy（CM） and macular pucker（MP）.An improvement was observed in the postoperative best-corrected visual acuity（BCVA）,as well as a decrement in central foveal thickness（CFT） in both groups（both of these being statistically significant;P=0.001）.In comparison between two groups,it was found that there was a significant improvement on BCVA and CFT in CM group than MP group（P=0.01）.Furthermore,the postoperative fundus findings regarding RPE alterations and macular edema were significantly higher in MP group when compared to the CM group（P=0.01）.CONCLUSION：ERM and internal limiting membrane peeling surgery can lead to a significant reduction of CFT and visual improvements in idiopathic ERM.A long-term ERM persistence will cause unrecoverable retinal damage and visual loss.

Displacement of the retina after idiopathic macular hole surgery with different internal limiting membrane peeling patterns

AIM:To explore retinal displacement after surgical treatment for idiopathic macular hole(IMH)with different internal limiting membrane(ILM)peeling patterns.METHODS:Totally 22 eyes from 20 patients with IMH were randomly allocated into two groups,N-T group(11 eyes)and T-N group(11 eyes).For patients in N-T group,ILM was peeled off from nasal to temporal retina.For patients in T-N group,ILM was peeled off from temporal to nasal retina.Preoperative,postoperative 1,3,and 6 mo,autofluorescence fundus images were collected for manual measurement of distances of fixed nasal(N),temporal(T),superior(S),and inferior(I)retinal points(bifurcation or crossing of retinal vessels)around the macula to the optic disc(OD).These were respectively defined as N-OD,T-OD,S-OD,and I-OD.The retinal displacement,macular holeclosure rate,and best corrected visual acuity(BCVA)were compared between the two groups after surgery.RESULTS:At postoperative 1,3,and 6 mo,the macula slipped toward the OD,manifested by the decreased T-OD,N-OD,S-OD,and I-OD(P<0.05).No significant difference was found in the T-OD,N-OD,S-OD,and I-OD between N-T group and T-N group.IMH closure rate was 100%both in N-T group and T-N group.There was no significant difference in BCVA between two groups(P<0.05).CONCLUSION:The macula slips toward the OD after successful macular hole surgery.The two different ILM peeling pattern show similar visual outcome and retinal displacement,which means ILM peeling directions are not the influencing factor of postoperative retinal displacement.

Vitrectomy with residual internal limiting membrane covering and autologous blood for a secondary macular hole:A case report

BACKGROUND Myopic foveoschisis(MF)is a common complication of pathological myopia.A macular hole(MH)usually results from the natural progression of MF and is a common complication of vitrectomy.Vitrectomy combined with residual internal limiting membrane(ILM)covering and autologous blood was effective for closing a secondary MH.CASE SUMMARY A 52-year-old woman presented to our clinic with a complaint of blurred vision in the right eye for 7 years.Her best corrected visual acuity(BCVA)was 20/100,axial length was 25.79 mm and standard equivalent refractive error was-10.5 dioptres.Preoperative optical coherence tomography revealed foveoschisis in the right eye.Vitrectomy with fovea-sparing ILM peeling was performed.An MH developed and gradually expanded 5 mo after the initial vitrectomy.Vitrectomy with residual ILM covering and autologous blood was performed.The MH closed 3 wk after the second vitrectomy.CONCLUSION Fovea-sparing ILM peeling can provide residual ILM for the treatment of MH secondary to vitrectomy for MF.Vitrectomy combined with residual ILM covering and autologous blood is effective for closing secondary MH and improving BCVA.

A Novel and Functional Artificial Bruch’s Membrane Made of Poly (ε-Caprolactone)/Gelatin for Retinal Pigment Epithelium Restoration

Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal implantation in patients. Methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Polycaprolactone (PCL), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. MTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch’s membrane and ARPE-19 morphology after 25 days of culture were studied with transmission and scanning electron microscopy. To evaluate expression changes in markers of ARPE-19 (RPE65 and ZO-1) qRT-PCR assays were realized. Data from three independent experiments were pooled and expressed as the mean SD. A confidence level of P 0.05 was considered to be statistically significant. Results ARPE-19 cells grew on PCL/Gelatin membranes mainly in PCL/30% gelatin combination, which had not cytotoxic effect. RPE65/cytokeratin-18/ and actin-positive ARPE-19 cells formed a correctly orientated monolayer of polygonal cells with morphological polarity. The apical cell surfaces exhibited abundant protruding microfolds. Moreover, zones of polygonal border look as if ARPE-19 cells fused among, suggesting the presence of tight junctions. The expression of RPE65 and ZO-1 was unchanged. Conclusions: PCL/30% Gelatine membranes may imitate the natural BM to such extent that they support RPE-cells and exhibited RPE-like morphology. The engineering of a human RPE monolayer with these artificial BM, emulating the in vivo retina, arouse their potential subretinal implantation in patients with wet age-related macular degeneration (AMD) where there is a rupture of the Bruch’s membrane.

Retinal pigment epithelium–Bruch’s membrane volume in grading of age-related macular degeneration

AIM:To assess the agreement of optical coherence tomography(OCT)algorithm-based retinal pigment epithelium–Bruch’s membrane complex volume(RBV)with fundus photograph-based age-related macular degeneration(AMD)grading.METHODS:Digital color fundus photographs(CFPs)and spectral domain OCT images were acquired from 96 elderly subjects.CFPs were graded according to Age-Related Eye Disease Study(AREDS)classification.OCT image segmentation and RBV data calculation were done with OrionTM software.Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs.RESULTS:RBV correlated with AMD grading(rs=0.338,P=0.001),the correlation was slightly stronger in early AMD(n=52;rs=0.432,P=0.001).RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs(1.05±0.20 vs 0.96±0.13 mm3,P=0.023).In multivariate analysis higher RBVs were associated significantly with higher total drusen(β=0.388,P=0.027)and pigmentation areas(β=0.319,P=0.020)in fundus photographs,whereas depigmentation area(β=-0.295,P=0.015)associated with lower RBV.CONCLUSION:RBV correlate with AMD grading status,with a stronger association in patients with moderate,non-late AMD grades.This effect is driven mostly by lesions with drusen or pigmentation.Lesions with depigmentation tend to have lower values.RBV is more comprehensive measurement of the key area of AMD pathogenesis,compared to sole drusen volume analysis.RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting,but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.

Negative effects of enlarging internal limiting membrane peeling for idiopathic macular hole surgery

AIM: To observe the effects of the different extents of internal limiting membrane(ILM) peeling on the surgical success and anatomical and functional outcomes of idiopathic macular hole(IMH).METHODS: In this retrospective cohort study, 36 patients were reviewed and divided into two groups according to the extent of ILM peeling: group A(18 patients), with the peeling area within one-half of the optic disc macular distance as the radius;group B(18 patients), with the peeling area larger than that of group A but did not exceed the optic disc macular distance as the radius. The main outcomes included the best corrected visual acuity(BCVA), light-adaptive electroretinography, macular hole(MH) closure rate, central macular thickness(CMT), retinal nerve fiber layer(RNFL) and ganglion cell complex(GCC) thickness [nine regions based on the Early Treatment of Diabetic Retinopathy Study(ETDRS) ring] before and 1, 3, and 6mo after surgery.RESULTS: The closure rate was 94.4%(17/18) both in groups A and B. The BCVA in both groups improved significantly compared with the preoperative values, but there was no difference between the two groups. The b-wave amplitude of the electroretinogram analysis was significantly improved in both groups compared to that of the preoperative period, with a greater increase in group A than in group B at 6mo(P=0.017). The CMT in both groups gradually decreased after surgery, and there was no difference between the two groups. The RNFL thickness of the temporal outer ring region in group B was significantly lower than that in group A at 3 and 6mo after surgery(P=0.010, 0.032). The GCC thickness of the temporal outer ring region in group B was significantly lower than that in group A at 6mo after surgery(P=0.038).CONCLUSION: Enlarging the extent of ILM peeling doesn’t affect the IMH closure rate and visual acuity recovery, but the greater the extent of peeling, the greater the damage to the inner retinal structures.

Foveal regeneration after resolution of cystoid macular edema without and with internal limiting membrane detachment:presumed role of glial cells for foveal structure stabilization

AIM: To document with spectral-domain optical coherence tomography the morphological regeneration of the fovea after resolution of cystoid macular edema(CME) without and with internal limiting membrane(ILM) detachment and to discuss the presumed role of the glial scaffold for foveal structure stabilization. METHODS: A retrospective case series of 38 eyes of 35 patients is described. Of these, 17 eyes of 16 patients displayed foveal regeneration after resolution of CME, and 6 eyes of 6 patients displayed CME with ILM detachment. Eleven eyes of 9 patients displayed other kinds of foveal and retinal disorders associated with ILM detachment. RESULTS: The pattern of edematous cyst distribution, with or without a large cyst in the foveola and preferred location of cysts in the inner nuclear layer or Henle fiber layer(HFL), may vary between different eyes with CME or in one eye during different CME episodes. Large cysts in the foveola may be associated with a tractional elevation of the inner foveal layers and the formation of a foveoschisis in the HFL. Edematous cysts are usually not formed in the ganglion cell layer. Eyes with CME and ILM detachment display a schisis between the detached ILM and nerve fiber layer(NFL) which is traversed by Müller cell trunks. ILM detachment was also found in single eyes with myopic traction maculopathy, macular pucker, full-thickness macular holes, outer lamellar holes, and glaucomatous parapapillary retinoschisis, and in 3 eyes with Müller cell sheen dystrophy(MCSD). As observed in eyes with MCSD, cellophane maculopathy, and macular pucker, respectively, fundus light reflections can be caused by different highly reflective membranes or layers: the thickened and tightened ILM which may or may not be detached from the NFL, the NFL, or idiopathic epiretinal membranes. In eyes with short single or multiple CME episodes, the central fovea regenerated either completely, which included the disappearance of irregularities of the photoreceptor layer lines and the reformation of a fovea externa, or with remaining irregularities of the photoreceptor layer lines. CONCLUSION: The examples of a complete regeneration of the foveal morphology after transient CME show that the fovea may withstand even large tractional deformations and has a conspicuous capacity of structural regeneration as long as no cell degeneration occurs. It is suggested that the regenerative capacity depends on the integrity of the threedimensional glial scaffold for foveal structure stabilization composed of Müller cell and astrocyte processes. The glial scaffold may also maintain the retinal structure after loss of most retinal neurons as in late-stage MCSD.

Efficacy of Phacovitrectomy Combined with Internal Limiting Membrane Peeling for Macular Diseases

Purpose:To observe the efficacy of vitrectomy with internal limiting membrane.(ILM) peeling combined with phacoemulsification with intraocular lens.(IOL) implantation in the treatment of cataract with co-existing macular diseases.Methods:A total of 28 cataract patients (28 eyes) with coexisting macular diseases were admitted to Aier Eye Hospital between May 2008 and May 2011.The clinical characteristics were analyzed in this study.Subjects included 6 men and 22 women,aged from 56 to 77 years (mean 64 years),with duration of disease ranging from 2 to 36 months (mean 9.3 months).All patients underwent phacoemulsification with implantation of a hydrophobic acrylic IOL into the capsular bag and pars plana vitrectomy with ILM peeling.Results:Postoperatively,patients underwent 3-to 18-months of follow-up.(mean 7.2 months).Only one eye had macular hole failing to close.Normal macular structure was restored in the other 27 eyes.The presenting visual acuity and best corrected visual acuity.(BCVA) did not differ significantly (t =-1.724,P =0.096),with the BCVA in 27 eyes.(96.4%).improving by 2 lines or more.The improvement in minimum angle of resolution.(MAR).was > 0.3 in 21 eyes,≥0.1 in 6 eyes and<0.1 in 1 eye.The mean spherical equivalent.(SE) was-4.67±5.98D preoperatively and-0.38±0.69D postoperatively (t=4.157,P<0.005).Conclusion:Combined phacovitrectomy surgery is a reliable and safe procedure in the treatment of cataract complicated by macular disease.