From the Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch at Galveston, Galveston, Texas.
Supported by a departmental grant by Research to Prevent Blindness, Inc., New York, New York.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Kapil G. Kapoor, MD, Department of Ophthalmology and Visual Sciences, 301 University Boulevard, Galveston, TX 77555. E-mail: Kaps2003@gmail.com
Since the advent of macular hole surgery in 1991 by Kelly and Wendel,1 several new techniques have emerged with the goal of improved visual acuity and anatomic outcome. These surgical techniques are focused on relieving anterior–posterior and/or tangential vitreoretinal traction on the macula coupled with retinal tamponade to promote retinal reapproximation to the retinal pigment epithelium. Circular epiretinal membrane may be an additional source of macular traction and can be identified by trypan blue and concurrently removed. More recently, it has been postulated that the internal limiting membrane (ILM) further contributes to macular traction and its identification with indocyanine green dye and concurrent removal has enhanced both anatomic and functional outcomes in some studies.2,3
Histopathologic studies of macular hole closure have enhanced our understanding, and particularly implicated a prominent role of fibroglial elements in this process.4 Several intraoperative adjuvant agents have been used to stimulate fibroglial proliferation and enhance macular hole closure, including thrombin, autologous serum, transforming growth factor-beta-2, biological tissue adhesive, and autologous platelet concentrate.5–7 Many of these adjuvants have demonstrated success in pilot studies and merit further investigation before coming into standard use. Autologous platelet concentrate demonstrated particular promise; it was initially reported to have a 95% anatomic success rate in a pilot study, which was later duplicated in a non-randomized study.8,9
The subsequent advent of ILM peeling assisted by indocyanine green improved macular hole closure rates, with studies demonstrating comparative macular hole closure rates with autologous platelets or ILM peeling of more than 95%.10,11 This may have contributed to the lack of routine use of autologous platelets. However, despite the success of ILM peeling, chronic macular holes (> 24 months) and inability to maintain prone positioning have remained two major markers for poor outcome.12,13 The purpose of our study was to evaluate the use of autologous platelet concentrate as an adjuvant to ILM peeling in the setting of chronic macular holes in patients unable to maintain prone positioning.
Patients and Methods
A retrospective case study was conducted on 13 eyes of 13 patients with stage 3 to 4 full-thickness macular holes (Table 1). All patients were pseudophakic, and each eye was treated with pars plana vitrectomy, ILM peeling, 0.1-cc autologous platelets, and 12% C3F8 gas tamponade. Autologous platelets were harvested as follows. On the day of surgery, 40 mL of the patient’s blood was mixed with acid citrate dextrose solution buffer. Under aseptic techniques, in conical tubes, the blood and acid citrate dextrose solution mixture was centrifuged twice (each time to draw off the supernatant) to isolate platelets. The platelet isolate was then re-suspended in 50 microliters of sterile 0.9% NaCl using a micropipette. The platelet solution was then placed in a sterile micro-centrifuge tube for transport to the operating room. In the operating room, the platelet solution was drawn into a sterile syringe ready for intravitreal injection. None of the patients underwent postoperative positioning. All patients had complete ophthalmic examinations preoperatively and 1 day and 1, 3, and 6 months postoperatively with optical coherence tomography. Main outcome measures were anatomic hole closure, final best-corrected visual acuity, and subjective quality of vision.
Table 1: Patient Demographics, Baseline Characteristics, and Postoperative Outcomes
All 13 patients completed 6 months’ follow-up. Chronicity of macular hole ranged from 2 to 5 years (Table 1). Eleven patients had idiopathic macular holes and two patients had traumatic macular holes. No patients had bilateral macular holes. Four patients were female, 9 were male, and mean patient age was 63 years. Macular hole closure was observed in all patients at 1 month postoperatively (Figs. 1, 2, 3, and 4). At 6 months, all patients experienced subjective improvement of visual acuity, typically characterized as improvement of an absolute central scotoma. Of 9 patients who had documented preoperative and postoperative Amsler grid testing, all had objective reduction in the size of the central scotoma. At 6 months postoperatively, 5 of 13 patients reported increased best-corrected visual acuity. There were no complications and no recurrences. Three patients experienced elevated intraocular pressure. All were successfully treated with topical aqueous suppressants and symptoms resolved by 3-month follow-up. No patients experienced retinal detachment, macular hole recurrence, or other complications in 6 months’ follow-up (Table 1). Partial retinal pigment epithelial atrophy was noted on examination of all patients, which is consistent in chronic macular holes; however, no patients experienced retinal pigment epithelial atrophy greater than 250 microns between preoperative examination and 6 months’ follow-up.
Figure 1. Full-thickness chronic macular hole depicted on optical coherence tomography.
Figure 2. Complete closure of macular hole demonstrated on postoperative month 1 examination.
Figure 3. Full-thickness chronic macular hole depicted on optical coherence tomography.
Figure 4. Postoperative optical coherence tomography shows full-thickness macular hole plugged with platelet concentrate.
Chronic macular holes and inability to maintain prone positioning are two challenges for successful macular hole repair.12,13 To the best of our knowledge, no study has combined both poor prognostic indicators of chronic macular hole and no face-down positioning in a single study.
Kelly and Wendel demonstrated a 22% anatomic closure rate for chronic macular holes without ILM peeling, and all patients maintained prone positioning for 7 to 10 days.1 Non-chronic macular hole closure rates with ILM peeling alone have ranged from 95% to 100% without positioning challenges.11,12 Kube et al. combined autologous platelets and ILM peeling and demonstrated an anatomic success rate of 94%; however, these were not chronic macular holes and patients in this study were able to successfully maintain prone positioning.14
The physical challenges of face-down positioning have been previously recognized and macular hole closure has been attempted with varying success with limited face-down positioning previously.15,16 Wu et al. reported a macular hole closure rate of 89% in non-chronic macular holes with ILM peeling alone and limited postoperative positioning.15 Merkur et al. used autologous platelets without ILM peeling and demonstrated a 92% hole closure rate with limited face-down positioning in non-chronic macular holes.16
Tranos et al. reported similar macular hole closure rates in phacovitrectomy with and without face-down positioning, although the group without prone positioning were advised to avoid the supine position for 10 days.17 Another study documented macular hole closure rates of 100% with phacovitrectomy, but still advised at least overnight face-down positioning.18 Tornambe et al. reported a macular hole closure rate of 79% in phacovitrectomy without any face-down positioning in their patients.19 Rubinstein et al. suggested combined phacovitrectomy was not essential to avoid prone positioning and their macular hole closure rate was 91.6% without face-down positioning in mostly pseudophakic patients with only vitrectomy.20 Data on positioning are highly varied, due partially to data coming from non-randomized trials or case series and partially to variable definitions of limited or no face-down positioning.
Our patients demonstrated a greater macular hole closure rate (100%) despite chronicity and inability to maintain prone positioning at all compared to other studies with only limited face-down positioning (89% to 92%) or only chronic macular holes (22% to 95%).
Conventionally, silicone oil tamponade has been used in macular hole repair in patients unable to maintain prone positioning, but with limited success. It has demonstrated lower rates of both anatomic and functional success when compared to gas tamponade, and also demonstrated higher rates of macular hole recurrence.21 Additionally, silicone oil tamponade requires a second surgery for removal, which can prove challenging in these patients with multiple comorbidities.
Previous studies have shown that both ILM peeling and autologous platelet concentrate may have beneficial roles in macular hole repair through different avenues, and the authors propose that they may have a synergetic role that is beneficial to exploit in certain cases. ILM peeling is beneficial because it aids in thoroughly removing any tangential tractional components, including any residual cortical vitreous, and ensures any tractional component from an epiretinal membrane is also relieved.22 ILM peeling itself enhances retinal compliance and also stimulates glial cell proliferation by surgical decapitation of Müller cells and astrocytes’ basal membrane, leading to edge reapproximation and ultimate hole closure.23 Gas tamponade with face-down positioning reinforces tractional relief provided by ILM peeling and helps consolidate edge reapproximation for hole closure.
Autologous platelets incite fibroglial proliferation, migration, and contraction of human retinal Müller cells that help plug the hole (Fig. 2).24 Because autologous platelets provide intrinsic adhesive support, it follows that they have enhanced macular hole closure despite an absence of face-down positioning in this study. Clearly, there is also considerable overlap in the healing mechanisms of ILM peeling and autologous platelets because ILM peeling also incites fibroglial proliferation and platelets also help maintain tractional relief, further supporting potential synergetic function. In cases with chronic macular holes and inability to maintain prone positioning, the current pilot data suggest that exploiting this synergy enhances outcomes.
The retinal pigment epithelial atrophy that accompanies chronic macular holes can limit improvement in visual acuity, but other troubling visual phenomena such as central scotomata can improve with the described surgical intervention.25 The improvement in central scotoma in patients with macular holes has been shown to lead to improved visual functioning such as improved eccentric fixation and visual perception.26,27
This study shows that autologous platelets may have a beneficial role as an adjunct to ILM peeling in chronic macular hole repair without prone positioning. To our knowledge, this is the first study investigating the macular hole closure rate of chronic macular holes and inability to maintain face-down positioning. The authors demonstrate a 100% anatomic success rate despite these relative contraindications and these results are superior to previous studies independently investigating chronicity or inability to maintain prone positioning. These results suggest a role for autologous platelets as a useful surgical adjunct in these cases. Large randomized control trials are needed to further elucidate the precise role of autologous platelets in macular hole repair.
- Kelly NE, Wendel RT. Vitreous surgery for idiopathic macular holes: results of a pilot study. Arch Ophthalmol. 1991;109:654–659. doi:10.1001/archopht.1991.01080050068031 [CrossRef]
- Rice TA. Internal limiting membrane removal in surgery for full-thickness macular holes. In: Madreperla SA, McCuen BW II, , eds. Macular Hole: Pathogenesis, Diagnosis, and Treatment. Boston: Butterworth-Heinemann; 1999:125–146.
- Haritoglou C, Reiniger IW, Schaumberger M, Gass CA, Priglinger SG, Kampik A. Five-year follow-up of macular hole surgery with peeling of the internal limiting membrane: update of a prospective study. Retina. 2006;26:618–622. doi:10.1097/00006982-200607000-00005 [CrossRef]
- Banker AS, Freeman WR, Azen SP, Lai MY. A multicentered clinical study of serum as adjuvant therapy for surgical treatment of macular holes. Vitrectomy for Macular Hole Study Group. Arch Ophthalmol. 1999;117:1499–1502. doi:10.1001/archopht.117.11.1499 [CrossRef]
- Kusaka S, Sakagami K, Kutsuna M, Ohashi Y. Treatment of full-thickness macular holes with autologous serum. Jpn J Ophthalmol. 1997;41:332–338. doi:10.1016/S0021-5155(97)00055-5 [CrossRef]
- Blumenkranz MS, Ohana E, Shaikh S, et al. Adjuvant methods in macular hole surgery: intraoperative plasma-thrombin mixture and postoperative fluid-gas exchange. Ophthalmic Surg Lasers. 2001;32:198–207.
- Claser BM, Michels RC, Kuppermann BD, Sjaarda RN, Pena RA. Transforming growth factor-beta 2 for the treatment of full-thickness macular holes: a prospective randomized study. Ophthalmology. 1992;99:162–172.
- Paques M, Chastang C, Mathis A, et al. Effect of autologous platelet concentrate in surgery for idiopathic macular hole: results of a multicenter, double-masked, randomized trial. Platelets in Macular Hole Surgery Group. Ophthalmology. 1999;106:932–938. doi:10.1016/S0161-6420(99)00512-6 [CrossRef]
- Ezra E, Gregor ZJMorfields Macular Hole Study Group. Surgery for idiopathic full-thickness macular hole: two-year results of a randomized clinical trial comparing natural history, vitrectomy, and vitrectomy plus autologous serum: Morfields Macular Hole Study Group Report No. 1. Arch Ophthalmol. 2004;122:224–236. doi:10.1001/archopht.122.2.224 [CrossRef]
- Cheung CMG, Munshi V, Mughal S, Mann J, Hero M. Anatomical success rate of macular hole surgery with autologous platelet without internal-limiting membrane peeling. Eye. 2005;19:1191–1193. doi:10.1038/sj.eye.6701733 [CrossRef]
- Brooks HL Jr, . Macular hole surgery with and without internal limiting membrane peeling. Ophthalmology. 2000;107:1939–1948. doi:10.1016/S0161-6420(00)00331-6 [CrossRef]
- Kumagai K, Furukawa M, Ogino N, Uemura A, Demizu S, Larson E. Vitreous surgery with and without internal limiting membrane peeling for macular hole repair. Retina. 2004;24:721–727. doi:10.1097/00006982-200410000-00006 [CrossRef]
- Stec LA, Ross RD, Williams GA, Trese MT, Margherio RR, Cox MS Jr, . Vitrectomy for chronic macular holes. Retina. 2004;24:341–347. doi:10.1097/00006982-200406000-00001 [CrossRef]
- Kube T, Hermel M, Dahlke C, Hutschenreuter G, Shrage N, Kirchhof B. Macular hole surgery: experience with autologous platelet concentrate and indocyanine green-assisted internal limiting membrane peeling [article in German]. Klin Monatsbl Augenheilkd. 2002;219:883–888. doi:10.1055/s-2002-36949 [CrossRef]
- Wu D, Ho LY, Lai M, Capone A Jr, . Surgical outcomes of idiopathic macular hole repair with limited postoperative positioning. Retina. 2011;31:609–611. doi:10.1097/IAE.0b013e318207ce93 [CrossRef]
- Merkur AB, Tuli R. Macular hole repair with limited nonsupine positioning. Retina. 2007;27:365–369. doi:10.1097/01.iae.0000242856.72514.5a [CrossRef]
- Tranos PG, Peter NM, Nath R, et al. Macular hole surgery without prone positioning. Eye (Lond). 2007;21:802–806. doi:10.1038/sj.eye.6702339 [CrossRef]
- Dhawahir-Scale FE, Maino A, Saha K, Mokashi AA, McLauchlan R, Charles S. To posture or not to posture after macular hole surgery. Retina. 2008;28:60–65. doi:10.1097/IAE.0b013e31813c68a2 [CrossRef]
- Tornambe PE, Poliner LS, Grote K. Macular hole surgery without face-down positioning: a pilot study. Retina. 1997;17:179–185. doi:10.1097/00006982-199705000-00001 [CrossRef]
- Rubinstein A, Ang A, Patel CK. Vitrectomy without postoperative posturing for idiopathic macular holes. Clin Experiment Ophthalmol. 2007;35:458–461. doi:10.1111/j.1442-9071.2007.01532.x [CrossRef]
- Tafoya ME, Lamber HM, Vu L, Ding M. Visual outcomes of silicone oil versus gas tamponade for macular hole surgery. Semin Ophthalmol. 2003;18:127–131. doi:10.1076/soph.22.214.171.124808 [CrossRef]
- Bainbridge J, Herbert E, Gregor Z. Macular holes: vitreoretinal relationships and surgical approaches. Eye (Lond). 2008;22:1301–1309. doi:10.1038/eye.2008.23 [CrossRef]
- Burmeister SL, Hartwig D, Limb GA, et al. Effect of various platelet preparations on retinal muller cells. Invest Ophthalmol Vis Sci. 2009;50:4881–4886. doi:10.1167/iovs.08-3057 [CrossRef]
- Anitua E, Andia I, Ardanza B, Nurden P, Nurden A. Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost. 2004;91:4–15.
- Valldeperas X, Wong D. Is it worth reoperating on macular holes?Ophthalmology. 2008;115:158–163. doi:10.1016/j.ophtha.2007.01.039 [CrossRef]
- Guez JE, Le Gargasson JF, Massin P, Rigaudiere F, Grall Y, Gaudric A. Functional assessment of macular hole surgery by scanning laser ophthalmoscopy. Ophthalmology. 1998;105:694–699. doi:10.1016/S0161-6420(98)94026-X [CrossRef]
- Sjaarda RN, Frank DA, Glaser BM, Thompson JT, Murphy RP. Assessment of vision in idiopathic macular holes with macular micro-perimetry using the scanning laser ophthalmoscope, Ophthalmology. 1993;100:1513–1518.
Patient Demographics, Baseline Characteristics, and Postoperative Outcomes
|Age (Y)||Gender||Laterality||MH Stage||Postop Resultsa||Complications||Preop VA (LogMAR)||Postop VA 1 Mo||Postop VA 6 Mo|