Long-term Structural and Functional Outcomes after Autologous Retinal Transplant Surgery for Complex Macular Hole

doi:10.21203/rs.3.rs-2372558/v1

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Long-term Structural and Functional Outcomes after Autologous Retinal Transplant Surgery for Complex Macular Hole

https://doi.org/10.21203/rs.3.rs-2372558/v1

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BACKGROUND

Vitrectomy and internal limiting membrane peeling has been the Gold Standard for macular hole treatment since the 90s with high closure rates for idiopathic macular holes, however those larger than 400 um or from other etiologies didn’t have such good outcomes. Over the years, different techniques were developed to increase anatomical and functional success rates, most of them using scaffold tissues; autologous retinal graft showed promising results in these cases, achieving higher closure rates and visual acuity improvement.

SUBJECTS AND METHODS

Observational prospective case series. 6 eyes treated with autologous retinal graft for complex macular holes were included. Baseline best corrected visual acuity (BCVA) and ocular coherence tomography (OCT) were collected. After 12 months of surgery, in all cases a complete ophthalmological examination, OCT, microperimetry, color vision and contrast sensitivity tests were performed at last follow-up.

RESULTS

6 eyes were included with a minimal diameter of 781.7 ± 157.4 um. Initial BCVA was 0.8 ± 0.1 logMAR; all eyes showed improvement or stability: 0.7 ± 0.2 (p: 0.455) at 12-months, that remained stable in most cases at the end of follow-up (p: 0.30), reaching an 83% anatomical and 67% functional success rates. Color vision tests were normal in most of the eyes with a mild tritanopia in one case, regarding contrast sensitivity 5 eyes showed improvement. Microperimetry show some generalized sensitivity loss and residual microescotomas, and fixation stability was variable.

CONCLUSIONS

Autologous retinal graft is an efficient technique for complex macular hole repair with good functional and anatomical outcomes.

Health sciences/Diseases/Eye diseases/Retinal diseases

Health sciences/Health care/Therapeutics/Surgery

Macular surgery has evolved in the last few years, since Kelly and Wendel described vitrectomy and internal limiting membrane peeling as the Gold Standard¹, due to the need of developing new techniques with better outcomes in patients with complex macular holes (minimal diameter > 600um, persistent or secondary to high myopia or blunt trauma) that has an estimated a 10 to 44% failure on closure^2,3; these techniques are based in the use of scaffold tissues which favors glial cells proliferation achieving higher closure rates, and therefore variable visual acuity improvement, the most used tissues are: Internal limiting membrane, anterior lens capsule and amniotic membrane, with good anatomic and functional outcomes, however sometimes this tissues are not available (for previous ILM peeling, pseufdophakia, etc)⁴. For this reason, a few years ago Grewal and Mahmoud proposed a new alternative by performing an autologous retinal transplant (ART) to close the hole and proved its efficacy and safety, initially in refractory myopic macular holes⁵, after the publication of their results the technique has been widely spread and their indications have been expanded to other etiologies^6,7,8. The exact mechanism of this technique is still unknown, however the theory behind its good outcomes relies in the graft’s ability to act as a scaffold tissue and a bridge between the hole borders, ectopic synaptogenesis has also been proposed^8,9, between retinal and donor tissue cells, but this haven’t been proved yet. However, its bigger impact in visual quantity and quality improvement and better structural cells integration area clear.

We present an observational case series of long-term structural and functional outcomes in macular holes treated with autologous retinal transplant.

An observational prospective case series of 6 patients treated with autologous retinal graft for complex macular holes, defined as: Idiopathic with minimal diameter ≥ 600um, secondary to with high myopia, recurrent or persistent (antecedent of previous vitrectomy and ILM peeling); all of them treated at Hospital Nuestra Señora de la Luz in Mexico City, from January 2019 to January 2020. The subjects with less than 12-month follow-up or had other ocular diseases (Glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration or trauma) were excluded. The study protocol was approved by our institutional board and the whole study adheres to the tenets set forth in the Declaration of Helsinki.

All surgeries were performed by the same surgeon; a three port 25G pars plana vitrectomy (Constellation; Alcon, Fort Worth, TX) digitally assisted with NGENUITY system (Alcon, Fort Worth, TX) was performed, with retrobulbar anesthesia. After trocars placement, central vitrectomy was performed in eyes with no previous surgery, internal limiting membrane (ILM) peeling was also performed or extended after dual blue (combined brilliant and trypan blue; DORC) dye solution was applied over the posterior pole. Then, donor area was delimited with diathermy (0.5 disc diameters bigger than the macular hole) outside vascular arcades on the superotemporal quadrant to avoid bleeding and then the graft was taken with retinal scissors until 90% of the circumference was complete, after that, perfluorocarbon was injected into the posterior pole and over the donor area to keep retina stable, and donor tissue was placed over the macular hole with retinal forceps assistance. Laser photocoagulation around donor area was applied, and air/fluid exchange was performed away from macular area and at the end of surgery silicon oil tamponade was left, and posteriorly removed one month after the first surgery.

All the included patients had complete files, including basal visual acuity and macular ocular coherence tomography (OCT), from before surgery. Complete ophthalmological clinical exams were performed in all cases at 12 months and at the end of their follow-up, including best corrected visual acuity (BCVA), color vision test (Farnswort test), contrast sensitivity test (Vision Contrast Test System), Microperimetry (COMPASS) and macular OCT (Heidelberg Spectralis) after 12 months of surgery.

6 eyes of 6 patients were included, 66% were females; with ages between 66 and 84-years-old. Macular hole etiology is summarized in table 1, most of our cases were idiopatic; with an average minimal diameter of 781.7 ± 157.4 um and a base diameter of 1651.8 ± 638.6 um (range: 1093–2856 um).

Anatomical success rate was 83% as proved by macular OCT, half of cases reached a type 2C closure; the rest were 0C, 2A or 2B (Fig. 1). Tissue integration was almost complete by first year; mostly inner retinal layers, with the presence of hypereflective spots into them in 2 cases. External limiting membrane (ELM) was restructured in 67% of eyes, but in only 50% (n:3) of cases ellipsoid zone (EZ) was recovered (with small disruptions in one patient) at 12-month follow-up (Fig. 1) this kept stable until last visit; showing that microstructure doesn’t change after 12 months.

Initial BCVA was 0.8 ± 0.1 logMAR; most of the eyes showed visual improvement or stability at 12-months (0.7 ± 0.2). Only two cases showed visual acuity worsening at the end of follow-up (0.8 ± 0.3) -one of them was a persistent macular hole and the other due to myopic maculopathy progression- and the rest remained stable, with at least 2 lines of improving reaching a 67% functional success rate. However, BCVA difference between baseline and final measure was not statistically different (p: 0.455 t test) and even thought there was at least one line of visual improvement in most cases the differences between baseline, 12 months (p 0.261) and the end of follow-up (p 0.30) did not showed any difference either (one-way ANOVA test).

Color vision test was normal in 67% of cases and one eye showed mild tritanopia, the last patient didn’t collaborate with the Farnsworth test. Contrast sensitivity showed improvement from baseline in 5 from 6 eyes (9.5 ± 10.8 with a visual acuity equivalent of 20/70 Snellen and spatial frequency of 3.0 ± 2.5).

Microperimetry showed an average sensitivity of -5.76 ± 6.6dB (range: -16.37 to + 0.58), with foveal involvement in 2 cases and parafoveal microscotomas in other two (Fig. 2). Fixation area was variable from 5.23° to 50.6° (21.5° ± 20.7°), and our high myopia patient results weren’t reliable. Total follow-up period was 23.8 ± 6.4 months.

Several studies proved autologous retinal graft efficacy in complex macular hole management; with anatomical success rates between 77 and 89% and variable visual acuity gains^5,6,7,8,9.

Graft integration can play an important role in functional recovery, which apparently is present almost immediately after surgery, and from the third month up, external limiting membrane reformation can be observed, in contrast ellipsoid zone reconstitution is not present in all cases, and if its present, it can be incomplete⁸. However, the gap closure seems to be enough to achieve a visual improvement. This could be possible based on the ectopic synaptogenesis theory, which implies that functional bipolar cells can expand their axons and stablish new connections with residual and donor tissue photoreceptors that are expressed in variable VA improvement^8,9,10; this theory is still under investigation.

Type of closure apparently influences visual acuity results, showing a better visual acuity in type 1 (Rossi classification) which is the most frequent closure pattern in small macular holes treated with conventional vitrectomy and ILM peeling technique. Type 2 closure is common in large macular holes, treated with the addition of scaffold tissues; and usually they evolve from 2A to 2C after a few months of the procedure; as part of tissue integration process¹¹ as it was showed at 12-month follow-up on most of our patients.

OCT changes in other publications showed an early integration of donor tissue, with an ELM reconstitution in 54% of cases in an average time of two months after the procedure, which was similar to our results; and some authors correlated this finding to better visual outcomes^6,7,8. Variable neurosensory retinal layers alignment was reported in other series^7,8,9; and reached 50% in ours.

Mycroperimetry changes has been studied for several authors in other macular hole repair techniques (ILM peeling and ILM inverted or free flap mostly)¹², they showed a reduction in central scotomas with residual paracentral microscotomas in some cases. Huang et al described a significant improvement on central sensitivity from 8.58 ± 3.05dB to 11.55 ± 2.72dB on large macular holes treated with free ILM flaps, this sensitivity improvement correlated with better visual acuity¹³. Fixation stability also improved in 90% of their cases, from 65.65 ± 17.28% to 78.59 ± 13.00%.

Moysidis et al in the largest case series yet, demonstrated an improved sensitivity response (6.7 ± 1.9 dB) in twelve of their patients, over the ART area, 3 of them had a final BCVA > 20/50 and better fixation stability. However, a formal analysis from microperimetry results wasn’t performed due to the small number of cases and their correlation with the macular hole etiology was not specified⁸. Their results contrasts with our series which showed a generalized sensitivity loss (-5.76 ± 6.6 dB) and an important fixation variability; this differences probably relay on macular hole etiologies, sizes and chronicity differences. Other authors showed sensitivity improvement mostly in the transplant borders¹⁴.

Color vision and contrast sensitivity tests usually are improved after vitrectomy and ILM peeling for macular hole surgery, as has been reported by Okamoto et al¹⁵, but there are not specific studies on ART technique and our results showed improvement form baseline in all cases; this may be possible trough ectopic synaptogenesis formations, which can be responsible for the partial functional restoration of neuroretinal cells (mostly bipolar cells and photoreceptors), however this theory needs deeper investigation.

We can conclude that autologous retinal graft is an efficient, safe and reproducible technique for complex macular hole repair; it shows an adequate tissue integration and external retinal layers reestablishment (mostly external limiting membrane and ellipsoid zone). This surgical technique has good functional outcomes not just regarding visual acuity, but quality, as proved by a better color perception and improved contrast sensitivity, stable at long-term follow-up.

AKNOWLEDGEMENTS

None

CONFLICT OF INTERESTS

None

FUNDING

None

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Table 1 is available in the Supplementary Files section.

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Table 1

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Version 1

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You are reading this latest preprint version

Long-term Structural and Functional Outcomes after Autologous Retinal Transplant Surgery for Complex Macular Hole

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Abstract

BACKGROUND

SUBJECTS AND METHODS

RESULTS

CONCLUSIONS

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Introduction

Subjects And Methods

Results

Discussion

Declarations

References

Tables

Additional Declarations

Supplementary Files

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