Dr.Prabu Baskaran, B13759, Dr.Pratyusha Ganne, Dr.Manavi Deokrishna Sindal, Dr.Nagesha
Abstract:
Context: Visual improvement after surgery for large macular holes depends on type of closure and also integrity of ellipsoid zone (EZ) and external limiting membrane (ELM). The analysis of decrement in defect size of these parameters by OCT gives insight into its impact on visual gain especially in closed macular holes.
Aims: We aim to analyse the defect size of ellipsoid zone and external limiting membrane in closed macular holes and to correlate the change with visual acuity change.
Settings and Design: Present study is subset analysis of ongoing Randomised controlled study comparing conventional ILM peeling technique versus inverted flap technique in large macular holes.
Methods and Material: We prospectively evaluated these parameters in 19 eyes which underwent perfluro N octane (PFCL) assisted single flap inversion technique for large macular holes. The EZ and ELM defect size was measured postoperatively and correlated with visual acuity change.
Statistical analysis used:Paired t-test and Wilcoxon signed rank test were used to compare the parameters between two visits. Pearson correlation was performed to find the relationship between the change in BCVA and change in OCT parameters.
Results: Total 19 eyes were analysed with mean hole diameter of 704µ.The mean BCVA improved from 0.73 to 0.45LogMAR units. Postoperatively, the mean EZD reduced from 1659.6 µ to 877 µ at 1month & 672 µ at 3 months. The mean ELMD reduced from 1440 µ to 877 µ at 1month & 600 µ at 3 months. The reduction in defect significantly correlates with visual acuity improvement at 1 & 3months.
Conclusions: Single flap inversion technique provides more physiological scaffold for restoration of ellipsoid zone and external limiting membrane. Potential for improvement in visual acuity was observed in subsequent visits and reflected in OCT as decreased defect size in ELM and ellipsoid zone.
Key-words: Ellipsoid zone; External limiting membrane; Internal limiting membrane; Inverted flap technique; Large macular hole.
Key Messages: ILM inversion technique aids in restoration of ellipsoid zone and ELM in follow-up visits after surgery for large macular holes. This is significantly correlating with the visual improvement observed on corresponding visits.
Introduction:
Macular hole surgery has come a long way since its inception. Small macular holes show good anatomical and visual results with the conventional ILM peeling technique. However, the same technique has not been very successful in large holes. Of late, various modifications of this technique have been tried in such cases.[1-3]Inverted internal limiting membrane (ILM) flap is one such technique which is being widely practiced for large and chronic macular holes.[4,5]Although the rates of closure have improved compared to the past, the visual gain following closure is debatable.
The ILM flap acts like scaffold for proliferation of glial tissue and thus assists closure of the hole.[6] In this regard, single flap inversion compared to a multilayered flap may have the advantage of preventing excess glial tissue proliferation. This may allow more physiological restoration of the retinal layers at the fovea. Theoretically, the Ellipsoid Zone (EZ) and External Limiting Membrane (ELM) restoration plays a key role in visual improvement following hole closure.[7] We prospectively analysed the ultrastructural changes at the fovea following macular hole surgery with single layer inversion technique and correlated the extent of restoration of EZ and ELM defects with the visual improvement.
Subjects and Methods:
This sample is a subset of a larger ongoing randomised control trial comparing inverted flap technique with the conventional technique in idiopathic large macular holes. This analysis was carried out on the subset of patients who underwent the inverted flap surgery. 21 eyes underwent Perfluro-n-Octane (PFO) assisted single layer ILM flap inversion technique for large macular holes (minimal hole diameter >500microns). Among the 21 eyes, 2 eyes had a second surgery (PFCL assisted ILM free flap technique) for non-closure of the hole. One hole failed to close and the other had persistent subretinal fluid (SRF) where ellipsoid zone and ELM defects could not be measured. Effectively, 19 cases were included which showed flat type closure. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters as detailed below were recorded pre-operatively and at 1,3 and 6 months follow up.
A standard 25 gauge pars plana vitrectomy was performed in all cases. After the initial core vitrectomy, posterior vitreous detachment was induced with or without the use of intravitreal triamcinolone acetonide. Brilliant blue dye (OCUBLUE PLUSTM, Brilliant blue G solution 0.05%w/v Aurolab, India) was used to stain the ILM. Once stained, the initial flap wasraised with the help of 27G curved membrane scraper (finesseTMFlex loop, Alcon) and further peeling was done with ILM forceps. Peeling was extended to 2 disc diameters (DD) around the hole. A small ILM flap (in one quadrant) around the edges of the holewas left. PFOwas injected over the disc covering the entire macula from arcade to arcade. The ILM flap was inverted and placed in the hole using a forceps under the PFO bubble. A careful fluid-air exchange (FAE) was done outside the PFO bubble first. Then, the PFO was completely aspirated. Air-gas (SF6-20%) exchange was done under visualisation. (Video clip 1) Postoperatively, face down positioning was advised for a week.
OCT parameters
All patients underwent comprehensive eye examination at 1st, 3rd and 6th months after the surgery. Macular scans were taken by spectral domain optical coherence tomography (SD OCT, Spectralis; Heidelberg engineering, Germany) at each visit. 8.7mm wide scans were taken passing through the fovea (768×496 pixels, 300 with ART mode (26): 35EDI protocol). The follow-up scans were taken with automated real-time tracking system. Data collected on OCT included: the minimum diameter of hole (MDH) measured as the distance at the narrowest portion of the macular hole in OCT cross sections; the EZD and ELMD defined as the distance (in microns) between the discontinuous lengths of the hyper reflective lines corresponding to EZ and ELM respectively. (Figure1)
Statistical analysis
Statistical analyses were carried out using SPSS statistical software for Windows, Version 21.0 (IBM Corp, Released 2013, Armonk, NY) and Microsoft Excel 2013 (Microsoft Corp, Redmond, WA). Paired t-test (for parametric data) and Wilcoxon signed rank test (for non-parametric data) were used to compare the parameters between two visits. Pearson correlation was performed to find the relationship between the change in BCVA and change in OCT parameters. A p value of < 0.05 was considered statistically significant.
Results:
A total of 19 eyes were analysed. All had type-1 closure and remained so till the last follow-up. All patients had 3 months follow up. However, only 10 eyes completed the 6th month follow up. The clinical and OCT parameters are detailed in Table 1.
The mean BCVA significantly improved from 0.74 logMAR (6/33 snellen equivalent) at baseline to 0.51 logMAR (6/19.5 snellen equivalent) at 1st month follow up, 0.42 logMAR (6/15.9 snellen equivalent) at 3rd month and 0.39 logMAR (6/14.7 snellen equivalent) at 6th month follow up.Half of the patients had a BCVA of 6/12 or better. The EZD and ELMD measured at 1st, 3rd and 6th month postoperatively showed a statistically significant decrease in size compared to the baseline. (Figures 2,3). There was a positive correlation between the improvement of vision at 3rd month follow up and the reduction in EZD/ELMD which reached statistically significant levels.(Table2, Figure 4) There was a similar trend observed at 6 months. However, it did not reach statistical significance due to a smaller sample size at 6 months.
Discussion:
Since macular hole surgery wasfirst described by Kelly and Wendel, the surgical techniques and visual results after vitrectomy and ILM peeling have significantly improved.[8] The sub foveal ultrastructural changes following a conventional macular hole surgery correlated well with improvement in visual acuity. However, literature on the same following an inverted flap surgery is sparse. OCT has helped analyse these ultrastructural changes after macular hole closure. Many studies have observed a direct correlation between photoreceptor integrity and visual improvement after surgery. Initial studies with stratus OCT showed that an increased irregularity of the photoreceptor layer and decreased photoreceptor thickness correlated poorly with visual gain.[9]Villate et all observed significant correlation between photoreceptor thickness and visual acuity gain (r=0.38, p-0.026). Authors assumed that the photoreceptor layer regeneration and realignment (seen as the hyper-reflective band in OCT) correlated with visual gain.[10]
First time, Michalewska studied foveal microstructure using spectral domain OCT in 68 eyes who underwent conventional ILM peeling technique.[11] He noted that the size of the linear defect in the photoreceptor segment layer statistically correlated with visual acuity gain. The higher resolution of newer OCT machines has helped us in understanding the foveal microstructure in greater detail and their effect on visual acuity improvements.
The advent of ILM inversion technique for large macular holes has improved both morphological and functional outcomes.[2] The ILM functions as scaffold for proliferation and migration of Muller cells. In addition neurotropic factors and bFGF contribute to macular hole closure. In a retrospective study, Lee et al studied 14 eyes with large and refractory macular holes who underwent multi-layered autologous ILM placement into the hole and observed glial cell proliferation resulting in complete hole closure.12 In such cases, exuberant proliferation of glial tissue occurs and hinders approximation of EZ and ELM defects.[13]
In contrast, single layer inversion technique has resulted in better anatomical restoration of foveal microstructure as compared to multi-layered flap insertion technique. Park et al retrospectively compared the results of ILM inversion versus ILM insertion in large macular holes (more than 500micron diameter) over 6 months. The author observed, better recovery of photoreceptor layers in ILM inversion technique as noted by better reduction in ELM and EZ defects compared to ILM insertion technique.[7]
The single layered inverted flap aided by PFCL has achieved similar results compared to ILM inversion. The 19 eyes included in this study had flap-closed macular holes as defined by Tornambe et al.[14] Our study prospectively analysed ultra-structural changes in the outer retina. We noted a gradual restoration of ELM and EZ zones over 3 to 6 months with corresponding improvements in visual acuity from baseline to 1, 3 and 6 months. The correlation of defect size with visual improvement highlights the potential for realignment and probable regeneration of ELM and EZ layers with a proper technique even in large macular holes.
The limitation of our study is a small sample size and a relatively shorter follow up period.
In conclusion, the EZ and ELM defects gradually reduced in size over 3-6 months following macular hole surgery. These reflected as improvement in visual acuity. There was no excessive gliosis at the fovea with this technique. Hence, single layered ILM flap technique not only increases the hole closure rate but also acts as a more physiological scaffold for the restoration of outer retinal layers and improves the visual acuity.
References:
1. Michalewska Z, Michalewski J, Dulczewska-Cichecka K, Adelman RA, Nawrocki J. Temporal inverted internal limiting membrane flap technique versus classic inverted internal limiting membrane flap technique: A Comparative Study. Retina. 2015 Sep;35(9):1844-50.
2. De Novelli FJ, Preti RC, RibeiroMonteiro ML, Pelayes DE, JunqueiraNóbregaM,Takahashi WY. Autologous Internal Limiting Membrane Fragment Transplantation for Large, Chronic, and Refractory Macular Holes. Ophthalmic Res. 2015;55(1):45-52.
3. Ozdek S, Baskaran P, Karabas L, Neves PP. A Modified Perfluoro-n-octane-Assisted Autologous Internal Limiting Membrane Transplant for Failed Macular Hole Reintervention: A Case Series. Ophthalmic Surg Lasers Imaging Retina. 2017 May 1;48(5):416-420.
4.Shin MK, Park KH, Park SW, Byon IS, Lee JE. Perfluoro-n-octane-assisted single-layered inverted internal limiting membrane flap technique for macular hole surgery. Retina. 2014 Sep;34(9):1905-10.
5. Michalewska Z, Michalewski J, Adelman RA, Nawrocki J. Inverted internal limiting membrane flap technique for large macular holes. Ophthalmology. 2010 Oct;117(10):2018-25.
6. Shiode Y, Morizane Y, Matoba R, Hirano M, Doi S, Toshima S, Takahashi K, Araki R, Kanzaki Y, Hosogi M, Yonezawa T, Yoshida A, Shiraga F. The Role of Inverted Internal Limiting Membrane Flap in Macular Hole Closure. Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4847-4855.
7. Park JH, Lee SM, Park SW, Lee JE, Byon IS. Comparative analysis of large macular hole surgeries using an internal limiting membrane: insertion technique versus inverted flap technique. Br J Ophthalmol. 2018 Apr 2. pii:bjophthalmol-2017-311770.
8. Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes. Results of a pilot study. Arch Ophthalmol. 1991 May;109(5):654-9.
9. Kitaya N, Hikichi T, Kagokawa H, Takamiya A, Takahashi A, Yoshida A.Irregularity of photoreceptor layer after successful macular hole surgery prevents visual acuity improvement. Am J Ophthalmol. 2004 Aug;138(2):308-10.
10. Villate N, Lee JE, Venkatraman A, Smiddy WE. Photoreceptor layer features ineyes with closed macular holes: optical coherence tomography findings andcorrelation with visual outcomes. Am J Ophthalmol. 2005 Feb;139(2):280-9.
11. Michalewska Z, Michalewski J, Cisiecki S, Adelman R, Nawrocki J. Correlation between foveal structure and visual outcome following macular hole surgery: a spectral optical coherence tomography study. Graefes Arch ClinExpOphthalmol. 2008 Jun;246(6):823-30.
12. Lee SM, Kwon HJ, Park SW, Lee JE, Byon IS. Microstructural changes in the fovea following autologous internal limiting membrane transplantation surgery for large macular holes. ActaOphthalmol. 2018 May;96(3):e406-e408.
13. Nagesha CK, Baskaran P, Dhoble P. Inverted macular hole edges following an inverted internal limiting membrane transplantation surgery for large macular hole. Indian J Ophthalmol. 2018 Feb;66(2):293-294.
14. Tornambe PE, Poliner LS, Cohen RG. Definition of macular hole surgery end points:elevated/open, flat/open, flat/closed. Retina. 1998:18(3):286-7.
Acknowledgement: None
| Table 1 | |||
| Parameter | Mean value | Range | P Value |
| Age of the patient (years) | 56.74±16.16 | 52 to 68 | – |
| Minimum diameter of hole (microns) | 700.68±122.93 | 514 to 944 | – |
| Pre-op BCVA (LogMAR) | 0.74±0.28 | 0.30 to 1.18 | – |
| Post-op BCVA at 3months (LogMAR) | 0.42±0.25 | 0.00 to 1.00 | 0.002 (pre-op vs post op) |
| Preop EZD (microns) | 1499.6±428.45 | 999 to 2287 | – |
| Post-op EZD at 3 months (microns) | 672.4±598.84 | 44 to 2146 | <0.0001 (pre-op vs post op) |
| Preop ELMD (microns) | 1454.7±456.71 | 791 to 2223 | – |
| Post-op ELMD at 3 months (microns) | 600.4±643.43 | 0 to 2204 | <0.0001 (pre-op vs post op) |
| BCVA:Best Corrected Visual Acuity; EZD: Ellipsoid zone defect; ELMD: External limiting membrane defect; vs: versus; *p<0.05 | |||
Table 1: Clinical parameters and visual acuity change before and after surgery
| Table 2 | ||||
| Change in BCVA compared to baseline | Change in EZ defect | Change in ELM defect | ||
| r value | p value | r value | p value | |
| 1month | 0.412 | 0.079 | 0.611 | 0.005* |
| 3 months | 0.527 | 0.044* | 0.594 | 0.02* |
| BCVA: Best corrected visual acuity ; EZ: Ellipsoid Zone; ELM :External Limiting Membrane; *p<0.05 | ||||
Table 2: Correlation table showing ELM and EZ defect change and its relation with visual acuity change.
Figure Legends
Figure 1: OCT cross section through macular hole showing discontinuous ends of ellipsoid zone (green arrowheads) and ELM (Yellow arrowheads).
Figure 2: Serial EDI-OCT scans through macula showing a) Full thickness macular hole b) Closed macular hole at 1 month postop with persistent EZD (yellow arrowheads) and ELMD. C) 6 months postop OCT showing segmental reappearance of ellipsoid zone (green arrowheads).
Figure 3Serial EDI-OCT scans through macula showing a) Full thickness macular hole b) 3months OCT showing closure of the hole with approximation of the ELM and EZ, c) 6 months OCT showing complete restoration of the ELM and EZ zone with a small microhole under the fovea.
Figure 4: Scatter plot correlation graph showing positive correlation between change in BCVA at 3 months and reduction of ELM (a) and EZ (b) defects.
Video clip 1: Video demonstrating internal limiting membrane peeling and PFCL assisted single layered flap inversion over large macular hole.
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