• Users Online: 252
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 29  |  Issue : 3  |  Page : 192-196

Role of internal limiting membrane peeling for cases of recalcitrant diabetic macular edema


1 Department of Ophthalmology, Andaman and Nicobar Islands Institution of Medical Science, Port Blair, Andaman and Nicobar Island, India
2 Army Hospital Research and Referral, New Delhi, India

Date of Web Publication30-Jan-2018

Correspondence Address:
Dr. Sujit Das
Department Of Ophthalmology, Andaman and Nicobar Islands Institution of Medical Science, Port Blair - 774 4104, Andaman and Nicobar Island
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_96_17

Rights and Permissions
  Abstract 


Background/Aims: To investigate the efficacy of internal limiting membrane (ILM) peeling following pars plana vitrectomy for cases of recalcitrant diabetic macular edema in terms of improved visual acuity and reduced central macular thickness (CMT).
Materials and Methods: A prospective randomized interventional study of 60 eyes with recalcitrant diabetic macular edema between age groups of 30–75 years of either sex were included if they are unresponsive to at least one intravitreal steroid after 4 weeks followed by at least one intravitreal antivascul©ar endothelial growth factors followed by conventional laser treatment after 8 weeks at least within or <8 weeks before enrollment into the study. The absence of macular ischemia and CMT of more than 350 μ were included. The main outcome measures were corrected and uncorrected visual acuity, reduction of CMT, early and postoperative complications, and intraocular pressure.
Results: The mean (standard deviation [SD]) of coherence tomography (OCT) was 558.3 (74.2) and 537.6 (52.6) in ILM and non-ILM group, respectively. On day 1, OCT was reduced to 419.0 in ILM peeling group (558.3–419.0, P< 0.001, statistically significant) and increased to 543.8 in non-ILM peeling group (537.6–543.8, P = 0.002, statistically significant) from baseline. The mean (SD) of best-corrected visual acuity (BCVA) at baseline in ILM peeling and non-ILM peeling were 1.24 (0.15) and 1.27 (0.15), respectively. The reduction in mean of BCVA at 6 and 12 weeks from baseline (1.24–1.16, P = 0.010 and 1.24–1.15, P = 0.014) was found to be statistically significant in ILM peeling whereas there is no change in the mean BCVA over 12 weeks.
Conclusion: ILM peeling gives satisfactory results in recalcitrant diabetic macular edema.

Keywords: Diabetic macular edema, diabetic retinopathy, recalcitrant diabetic macular edema


How to cite this article:
Das S, Maggon R. Role of internal limiting membrane peeling for cases of recalcitrant diabetic macular edema. Kerala J Ophthalmol 2017;29:192-6

How to cite this URL:
Das S, Maggon R. Role of internal limiting membrane peeling for cases of recalcitrant diabetic macular edema. Kerala J Ophthalmol [serial online] 2017 [cited 2018 Sep 19];29:192-6. Available from: http://www.kjophthal.com/text.asp?2017/29/3/192/224307




  Introduction Top


Diabetic macular edema is the largest cause of visual acuity loss in nonproliferative diabetic retinopathy and is the most important challenge in ophthalmology. Disruption of blood retinal barrier, pericyte loss,[1] increased vascular permeability and vitreo-retinal traction are all together is responsible for the development of diabetic macular edema. Disruption and increased permeability resulting in swelling of the macula with the formation of cyst-like changes called as cystoids macular edema. Accumulation of fluid occurs in the outer plexiform and inner plexiform layer of the retina. Approximately 10% diabetic population has Type 1 and 90% has Type 2 diabetes.[2],[3] Duration of the disease is a significant risk factor for the development of diabetic retinopathy and its complications. Early detection and quantification are therefore of major importance in evaluation of diabetic patients. Macular ischemia resulting from the closure of retinal capillaries stimulates the release of vascular endothelial growth factors (VEGF) which in turn increases vascular permeability. Diabetic macular edema also exacerbated due to persistent vitreomacular traction by residual cortical on the macula after posterior vitreous detachment (PVD), thickened and taut posterior hyaloid that may or may not be adherent to internal limiting membrane (ILM). The presence of a thick taut posterior hyaloid membrane exerting traction on the macula resulting in shallow macular detachment could be another cause for recalcitrant diabetic macular edema.[4],[5],[6],[7],[8] In the presence of hypertension, hyperlipidemia, and chronic renal failure, the degree of fluid and hard exudates accumulation under the macula is aggravated leading to significant visual impairment and making response to laser photocoagulation poor. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenic process of diabetic macular edema gave reason for intravitreal steroid injection. Laser photocoagulation decreases oxygen consumption by destroying photoreceptors and thereby reducing the release of endothelial growth factors. Combination therapy with intravitreal steroid and ani-vascular endotheleal growth factor (VEGF) reduces [7] the foveal thickness and allows more precise and effective macular laser photocoagulation with lower energy level needed. Pars plana vitrectomy (PPV) with ILM peeling promotes migration of cells, egress of extracellular fluid and blood out of the retina and toward the vitreous cavity. Reduction in retinal thickening and improvement in oxygenation should theoretically improve visual acuity.[9],[10]


  Materials and Methods Top


This was a prospective randomized interventional study of 60 eyes/patients with recalcitrant diabetic macular edema between age groups of 30–75 years of either sex attending to the eye outpatient department during a study period of 2 years from June 2013 to June 2015. Eyes were included if they are unresponsive to at least one intravitreal steroid (triamcinolone acetonide) after 4 weeks followed by at least one intravitreal anti-VEGF followed by conventional laser treatment after 8 weeks at least within or <8 weeks before enrollment into the study. Inclusion criteria were (1) diabetic age was >10 years with good diabetic control (HbA1C <7), (2) presence of clinically significant macular edema demonstrated clinically and angiographically, (3) clear media with the absence of significant lens opacity, (4) postlaser status with a history of at least 1 focal laser by retinal specialist at 8 weeks before enrollment, (5) stable lipid profile, (6) absence of macular ischemia, and (7) optical coherence tomography (OCT) evidence of central macular thickness (CMT) more than 350 μ. Thus, only eyes with recalcitrant diabetic macular edema that have been refractory to standard laser treatment without a taut posterior hyaloid on OCT were included in this study. Patients with poor diabetic control, overt nephropathy, dyslipidemia, significant lens opacity, and presence of macular ischemia on fundus fluorescein angiography (FFA) were excluded from this study. Preoperative assessment includes assessment of diabetic control by HbA1C, presence of associated hypertension and hyperlipidemia, Snellen's uncorrected and best-corrected visual acuity (BCVA), Goldman applanation tonometry, slit lamp examination, posterior segment examination, FFA, and OCT. Patients were randomized to undergo PPV with or without ILM peeling. During vitrectomy, the ILM were peeled in 28 eyes (ILM peeled Group-I) while in remaining 28 eyes, ILM was not peeled (ILM preserved Group-II). All patients underwent 23-gauge PPV using machine (Alcon 800 CS, Fort worth, Texas, USA) plus intravitreal triamcinolone acetonide 4 mg/0.1 ml to delineate the posterior cortical vitreous and to aid in induction of PVD. Staining of ILM was done with brilliant blue. Peeling of ILM was initiated by creating a tear close to the optic disc. By the technique of maculorhexis, ILM peeling was completed and membrane was removed with intraocular forceps. Patients were followed till 12 weeks; 1st follow up was after 1 day, 2nd follow up after 7 days, 3rd follow up was after 6 weeks, and 4th follow-up after 12 weeks. On each visit visual acuity, intra-ocular pressure and central macular thickness was carried out to see the results.


  Results Top


A total of 60 (44 males and 16 females) patients were enrolled in the study with age range of 30–75 years, duration of diabetes of 7–20 years (mean duration 13.5 years), and mean HbA1c of 6.7.

In this study, 60 patients were randomized into either ILM peeling (n = 30) or non-ILM peeling group (n = 30). The mean (standard deviation [SD]) age of patients in ILM peeling and non-ILM peeling were 60.2 (6.3) and 61.7 (6.7), respectively. Fourteen were males and 16 were females in the ILM peeling, and 15 were males and 15 were females in the non-ILM peeling group. The associated comorbidities found were hypertension alone in 11 and 14 patients, hyperlipidemias in 11 and 5 patients, hypertension and hyperlipidemias in 4 patients and 4 patient, chronic renal failure in 4 and 4 patients, and no associated comorbidity were in 0 and 3 patients in ILM peeling and non-ILM peeling group, respectively. All the baseline variables such as age, gender, duration of disease, associated comorbidities, and HbA1c were not statistically significant, as shown in [Table 1].
Table 1: Baseline characteristics between the groups

Click here to view


The comparison of mean OCT values between and within the groups is shown in [Table 2] and [Table 3], respectively. The mean (SD) of OCT was 558.3 (74.2) and 537.6 (52.6) in ILM and non-ILM group, respectively. On day 1, OCT was reduced to 419.0 in ILM peeling group (558.3–419.0, P < 0.001, statistically significant) and increased to 543.8 in non-ILM peeling group (537.6–543.8, P = 0.002, statistically significant) from baseline. The mean OCT values were significantly reduced after ILM peeling over 12 weeks from baseline whereas fluctuating and increasing trend in OCT values was observed in non-ILM peeling group.
Table 2: Optical coherence tomography (í) between groups

Click here to view
Table 3: Optical coherence tomography (í) within group comparison

Click here to view


[Table 4] and [Table 5] shows the mean BCVA values between and within the group, respectively. The mean (SD) of BCVA at baseline in ILM peeling and non-ILM peeling were 1.24 (0.15) and 1.27 (0.15), respectively, and the difference was not statistically significant. The reduction in mean of BCVA at 6 and 12 weeks from baseline (1.24–1.16, P = 0.010 and 1.24–1.15, P = 0.014) was found to be statistically significant in ILM peeling whereas there is no change in the mean BCVA over 12 weeks [Table 5] in non-ILM peeling group.
Table 4: Best-corrected visual acuity between the groups

Click here to view
Table 5: Best-corrected visual acuity within-group comparison

Click here to view



  Discussion Top


Diabetic macular edema is the largest cause of visual acuity loss in diabetic retinopathy. It affects central vision from the early stages of retinopathy and is the most frequent complication of diabetic retinopathy, particularly in Type 2 diabetic retinopathy. It is the amount and type of edema that determines the modality of treatment employed and prognosis of the visual outcome. This explains the emergence of OCT as a key investigation in the diagnosis and management of diabetic macular edema. Hyperglycemia-induced changes in tight junction, pericyte loss, increased vascular permeability, and vitreomacular traction are implicated in its development. Diabetic macular edema also exacerbated due to persistent vitreomacular traction by residual cortical on the macula after PVD, thickened and taut posterior hyaloid that may or may not be adherent to ILM. The presence of a thick taut posterior hyaloid membrane exerting traction on the macula resulting in shallow macular detachment could be another cause for recalcitrant macular edema in diabetes. In the presence of hypertension, hyperlipidemia, and chronic renal failure, the degree of fluid and hard exudates accumulation under the macula is aggravated leading to significant visual impairment and making response to laser photocoagulation poor. Until recent years, macular laser photocoagulation was the only available therapy. The awareness that inflammation is an important factor in the pathogenic process of diabetic macular edema gave reason for intravitreal steroid injection. Laser photocoagulation decreases oxygen consumption by destroying photoreceptors and thereby reducing the release of endothelial growth factors. Combination therapy with intravitreal steroid and anti-VEGF reduces the foveal thickness and allows more precise and effective macular laser photocoagulation with lower energy level needed. PPV with ILM peeling promotes migration of cells, egress of extracellular fluid and blood out of the retina and toward the vitreous cavity. Reduction in retinal thickening and improvement in oxygenation should theoretically improve visual acuity.

In July 2010, Mohmmad Dehghan et al. reported possible association between ILM peeling and reduction of central macular edema. They performed ILM peeling in 1 eye of clinically significant diabetic macular edema with mean age of 59.6 (range 55–68) years and followed for a mean period of 4.9 ± 1.0 (range 4–6) months. Mean BCVA at final examination was 0.82 ± 0.18 logMAR which was not significantly better than its preoperative value of 1.00 ± 0.80logMAR (P = 0.959). Visual acuity improved by at least 2 lines in 3 years (25%), remained stable in 7 eyes (58%), and decreased by at least 2 lines in 2 eyes (17%). Mean CMT was 315 ± 95 μ, which was significantly less than its preoperative value of 467 ± 107 μ (P = 0.004). Complication includes vitreous hemorrhage in 2 and cataract progression in 5 eyes. Pars plana vitrectomy with internal limiting membrane peeling reduce macular thickness but does not significantly improve visual acuity- as it is seen in 53% patients of Group-I. Results were not significantly significant different (Group I: mean decrease logMAR 95% CI [0.06; 0.32], Group II [−0.02; 0.11]). OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM peeling removal (Group I: mean change 95% CI [−0.208.95 μ; −78.05 μ], Group-II −80.90 μ; +59.17 μ).

As per author information, Hartley 2008, ILM peeling in diabetic macular edema showed reduction in edema when measured by OCT in the majority of eyes, but visual acuity outcomes showed minimal improvement compared to baseline. These results suggest the efficacy of PPV with ILM peeling for eyes with diabetic macular edema has not been well established and should be reserved for therapy with selected cases. They performed ILM peeling in 4 eyes of 23 patients. Duration of diabetic macular edema ranged from 1 to 93 months. Mean preoperative logMAR vision was 0.782 (range, 0.30–1.82). Mean logMAR visual acuity at final follow-up was 0.771 (range, 0.10–2.0). At last follow-up, 255 of eyes had > or + 2 line increase in visual acuity from baseline, 54% of eyes had no improvement in visual acuity, and 21% of eyes had > or + 2 line decrease in visual acuity. In nine (9) eyes it was seen that there was an overall reduction of central macular thickness post-operatively (141 micron at 6 months and 120 micron in last follow-up). Postoperative complications includes progression of cataract in 6 (60%) of 10 phakic eyes, postoperative intraocular pressure ≥30 mmHg in 6 (24%) eyes, and postoperative vitreous hemorrhage in 2 (8%) eyes.

The early results of this ongoing study suggest that PPV with ILM peeling for recalcitrant diabetic macular edema is safe procedure that provides anatomic improvement but visual acuity outcomes showed minimal improvement compared to baseline with chronic macular edema unresponsive to standard conventional therapy because of physiological damage already done by diabetes.


  Conclusion Top


Diabetic macular edema is the significant cause of visual acuity loss in diabetic retinopathy that affects the central vision loss, particularly in Type 2 diabetes. It is the amount and type of edema that determines the modality of treatment employed and prognosis of the visual outcome, thus explaining the emergence of OCT in the diagnosis and management of diabetic macular edema.

The mean OCT values were significantly reduced after ILM peeling over 12 weeks from baseline whereas fluctuating and increasing trend in OCT values was observed in non-ILM peeling group [Figure 1] and [Figure 2].
Figure 1: Preoperative left eye central macular thickness

Click here to view
Figure 2: Postoperative reduction of central macular thickness

Click here to view


The reduction in mean of BCVA at 6 and 12 weeks from baseline was found to be statistically significant in ILM peeling whereas there was no change in the mean BCVA over 12 weeks in non-ILM peeling group.

All the baseline variables such as age, gender, duration of disease, associated comorbidities, and HbA1c were not statistically significant. FFA performed after 6 and 12 weeks after the procedure was showing progressively decreasing leak [Figure 3]. The fundus picture looked better steadily with progressively reducing retinal edema and resumption of hard exudates. The early result of this ongoing study suggests that PPV with ILM peeling for recalcitrant diabetic macular edema is a safe procedure and provides anatomic and structural improvement, but the visual acuity outcome showed minimal improvement compared to baseline results with recalcitrant diabetic macular edema unresponsive to standard conventional therapy.
Figure 3: Preoperative and postoperative picture of fluorescein angiography shows reduction in leakage

Click here to view


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Addison DJ, Garner A, Ashton N. Degeneration of intramural pericytes in diabetic retinopathy. Br Med J 1970;1:264-6.  Back to cited text no. 1
    
2.
Paulus YM, Gariano RF. Diabetic retinopathy: A growing concern in an aging population. Geriatrics 2009;64:16-20.  Back to cited text no. 2
    
3.
Klein R, Klein BE, Moss SE, Cruickshanks KJ. The wisconsin epidemiologic study of diabetic retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology 1998;105:1801-15.  Back to cited text no. 3
    
4.
Takagi H, Otani A, Kiryu J, Ogura Y. New surgical approach for removing massive foveal hard exudates in diabetic macular edema. Ophthalmology 1999;106:249-56.  Back to cited text no. 4
    
5.
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The wisconsin epidemiologic study of diabetic retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol 1984;102:527-32.  Back to cited text no. 5
    
6.
Dillinger P, Mester U. Vitrectomy with removal of the internal limiting membrane in chronic diabetic macular oedema. Graefes Arch Clin Exp Ophthalmol 2004;242:630-7.  Back to cited text no. 6
    
7.
Murata T, Ishibashi T, Khalil A. Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmol 1995;27:48-52.  Back to cited text no. 7
    
8.
Williams R, Airey M, Baxter H. Epidemiology of diabetic retinopathy and macular edema: A systematic review. Dev Ophthalmol 2004;18:963-83.  Back to cited text no. 8
    
9.
Rosenblatt BJ, Shah GK, Sharma S, Bakal J. Pars plana vitrectomy with internal limiting membranectomy for refractory diabetic macular edema without a taut posterior hyaloid. Graefes Arch Clin Exp Ophthalmol 2005;243:20-5.  Back to cited text no. 9
    
10.
Lewis H, Abrams GW, Blumenkranz MS, Campo RV. Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. Ophthalmology 1992;99:753-9.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed266    
    Printed15    
    Emailed0    
    PDF Downloaded47    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]