Ophthalmic Surgery, Lasers and Imaging Retina

Case Report 

Topical Aqueous Suppression and Closure of Idiopathic Full-Thickness Macular Holes

Daniel Su, MD; Anthony Obeid, MD, MPH; Jason Hsu, MD

Abstract

Hydration of retinal tissue has been proposed as a potential model of macular hole (MH) formation in addition to tractional forces of the vitreous and internal limiting membrane (ILM). Carbonic anhydrase inhibitors have previously been utilized in the treatment of cystoid macular edema in outer retinal diseases. There has been recent interest in the use of topical aqueous suppression as a potential medical therapy for MHs. In this case series, four eyes with small (< 300 μm) full-thickness MHs were treated with topical dorzolamide-timolol for 1 month. Two eyes achieved closure of the MH without surgical intervention, whereas the other two required pars plana vitrectomy with ILM peel. Future studies are required to investigate the role of topical aqueous suppression in the management of MHs.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:e38–e43.]

Abstract

Hydration of retinal tissue has been proposed as a potential model of macular hole (MH) formation in addition to tractional forces of the vitreous and internal limiting membrane (ILM). Carbonic anhydrase inhibitors have previously been utilized in the treatment of cystoid macular edema in outer retinal diseases. There has been recent interest in the use of topical aqueous suppression as a potential medical therapy for MHs. In this case series, four eyes with small (< 300 μm) full-thickness MHs were treated with topical dorzolamide-timolol for 1 month. Two eyes achieved closure of the MH without surgical intervention, whereas the other two required pars plana vitrectomy with ILM peel. Future studies are required to investigate the role of topical aqueous suppression in the management of MHs.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:e38–e43.]

Introduction

Idiopathic full-thickness macular holes (FTMHs) are generally accepted to result from tractional forces at the vitreoretinal interface.1 More recently, hydration of retinal tissue has been proposed as a potential contributor to macular hole (MH) formation.2 Using serial optical coherence tomography (OCT) images, other investigators have shown that MH development may follow discrete stages of tractional disruption of the fovea followed by progressive hydration of the perifoveal area leading to enlargement of the MH.3

Aqueous suppression with carbonic anhydrase inhibitors in either oral (acetazolamide) or topical (dorzolamide [Trusopt; Merck, Kenilworth, NJ]) form has been shown to be efficacious in the treatment of cystoid macular edema (CME) in the setting of retinitis pigmentosa.4,5 The exact mechanism by which CME is reduced in this setting is unclear but has been proposed to be related to improved fluid resorption by the retinal pigment epithelium (RPE).6 It has been hypothesized that the dehydration of CME may lead to morphological improvement and even closure of FTMHs. We also theorized that maximally decreasing aqueous production with the addition of a beta-blocker might reduce fluid flux through the hole and perhaps augment this dehydration. Here we report four consecutive cases of idiopathic small MHs (< 300 μm) that were treated initially with topical aqueous suppression and their outcomes.

Case Reports

Case 1

An 81-year-old man with a lamellar hole and wet macular degeneration in the left eye presented 10 weeks after an intravitreal injection with a new FTMH. Visual acuity (VA) was 20/200, which was unchanged from baseline. OCT revealed a FTMH with mild perifoveal cystoid changes (Figure 1A). The patient deferred surgery given there was no noticeable change in vision. Topical dorzolamide-timolol (Cosopt; Akorn Pharmaceuticals, Lake Forest, IL) was started twice daily. One month later, the hole persisted with increased perifoveal swelling (Figure 1B) and the patient underwent pars plana vitrectomy (PPV) with ILM peeling. OCT at 1 month after surgery showed a closed MH with decreased macular edema (Figure 1C). Vision was stable at 20/200.

(A) Optical coherence tomography image of an 81-year-old man with neovascular macular degeneration who presented with a full-thickness macular hole (MH) 10 weeks after intravitreal injection. Mild perifoveal cystoid changes were present. (B) One month after initiation of topical dorzolamide-timolol with a persistent MH and worsening perifoveal swelling. (C) Closure of the MH after pars plana vitrectomy with internal limiting membrane peeling.

Figure 1.

(A) Optical coherence tomography image of an 81-year-old man with neovascular macular degeneration who presented with a full-thickness macular hole (MH) 10 weeks after intravitreal injection. Mild perifoveal cystoid changes were present. (B) One month after initiation of topical dorzolamide-timolol with a persistent MH and worsening perifoveal swelling. (C) Closure of the MH after pars plana vitrectomy with internal limiting membrane peeling.

Case 2

A 70-year-old man with a history of retinal detachment in the right eye status post PPV and scleral buckle was found to have a new FTMH with associated cystoid changes and a mild epiretinal membrane (ERM) at his postoperative month 1 visit (Figure 2A). No residual gas tamponade was present. VA was 20/200. The patient was started on dorzolamide-timolol twice daily. One month later, VA improved to 20/80 and OCT revealed closure of the FTMH with a stable mild ERM (Figure 2B). The MH remained closed after 1 year with stable VA of 20/50 (Figure 2C).

(A) Right eye optical coherence tomography of a 70-year-old man with a recent vitrectomy for macula-off rhegmatogenous retinal detachment revealing a new macular hole (MH). (B) Closure of the MH 1 month after topical dorzolamide-timolol with mild persistent outer-retinal disruptions. (C) Reconstitution of outer-retinal architecture 1 year later with improvement of VA of 20/50.

Figure 2.

(A) Right eye optical coherence tomography of a 70-year-old man with a recent vitrectomy for macula-off rhegmatogenous retinal detachment revealing a new macular hole (MH). (B) Closure of the MH 1 month after topical dorzolamide-timolol with mild persistent outer-retinal disruptions. (C) Reconstitution of outer-retinal architecture 1 year later with improvement of VA of 20/50.

Case 3

A 55-year-old woman with a posterior vitreous detachment (PVD) and associated vitreous hemorrhage in her right eye 2 months prior presented with a small FTMH with large perifoveal cysts (Figure 3A). VA was 20/200. Dorzolamide-timolol was started twice daily with no improvement after 1 month (Figure 3B). The patient underwent surgery with successful closure of the FTMH. Two months later, her VA improved to 20/50 with a small pocket of subfoveal fluid (Figure 3C). Six months after surgery, the hole remained closed with resolution of subretinal fluid and VA of 20/25 (Figure 3D).

(A) Full-thickness macular hole (MH) in a 55-year-old woman with large perifoveal cysts. (B) No improvement was seen 1 month after topical aqueous suppression with dorzolamide-timolol. (C) Closure of the MH after vitrectomy with internal limiting membrane removal. A small pocket of subfoveal fluid was present. (D) Six months after surgery with resolution of subfoveal fluid.

Figure 3.

(A) Full-thickness macular hole (MH) in a 55-year-old woman with large perifoveal cysts. (B) No improvement was seen 1 month after topical aqueous suppression with dorzolamide-timolol. (C) Closure of the MH after vitrectomy with internal limiting membrane removal. A small pocket of subfoveal fluid was present. (D) Six months after surgery with resolution of subfoveal fluid.

Case 4

A 63-year-old woman with a history of a FTMH successfully repaired in her left eye presented with a small FTMH in her right eye with a new partial PVD as evidenced by vitreous separation from the macula and an overlying operculum. VA was 20/60, decreased from her baseline of 20/30. OCT demonstrated a small FTMH without appreciable cystoid changes (Figure 4A). One month after starting twice-daily topical dorzolamide-timolol, her vision improved to 20/40 with closure of the FTMH (Figure 4B). The partial PVD appeared stable both on examination and OCT without progression to a complete PVD. A small pocket of subfoveal fluid present on OCT resolved 4 months later without additional improvement in her VA (Figure 4C).

(A) Preceding optical coherence tomography of the right eye in a 63-year-old woman. (B) A new small macular hole (MH) without perifoveal swelling developed with a new partial posterior vitreous detachment (PVD). A small operculum (arrow) is present on the hyaloid face. (C) Closure of MH with improved vision 1 month after initiation of topical dorzolamide-timolol. A small pocket of subfoveal fluid or outer-retinal cavitation was present. The partial PVD and operculum appeared stable (arrow). (D) Persistent focal outer-retinal disruption was present along with stable partial PVD and operculum (arrow) 4 months later.

Figure 4.

(A) Preceding optical coherence tomography of the right eye in a 63-year-old woman. (B) A new small macular hole (MH) without perifoveal swelling developed with a new partial posterior vitreous detachment (PVD). A small operculum (arrow) is present on the hyaloid face. (C) Closure of MH with improved vision 1 month after initiation of topical dorzolamide-timolol. A small pocket of subfoveal fluid or outer-retinal cavitation was present. The partial PVD and operculum appeared stable (arrow). (D) Persistent focal outer-retinal disruption was present along with stable partial PVD and operculum (arrow) 4 months later.

Clinical data, including duration of treatment with topical dorzolamide-timolol, closure of MH, duration to closure, presence of PVD, and VA, were recorded (Table 1). OCT images were reviewed for various characteristics pre- and post-treatment with topical dorzolamide-timolol (Table 2).

Clinical Characteristics of Patients/Eyes Receiving Dorzolamide-Timolol for a Full Thickness Macular Hole

Table 1:

Clinical Characteristics of Patients/Eyes Receiving Dorzolamide-Timolol for a Full Thickness Macular Hole

Optical Coherence Tomography Characteristics of Eyes Receiving Dorzolamide-Timolol for a Full-Thickness Macular Hole

Table 2:

Optical Coherence Tomography Characteristics of Eyes Receiving Dorzolamide-Timolol for a Full-Thickness Macular Hole

Discussion

Spontaneous closure rates of FTMHs are reported in the range of 2.7% to 6.8% in eyes without treatment.7,8 In this small case series of four consecutive eyes, we observed closure of 50% of the FTMH without surgical intervention. In both cases of closure with topical dorzolamide-timolol, associated improvement in vision was observed and stable up to 20 months after closure.

In support of the hydration theory in the pathogenesis of FTMHs, Gentile et al. performed serial OCTs and demonstrated hydration of the outer retina resulting in progression to FTMH after an initial ILM defect caused by vitreofoveolar traction.3 Of the two cases in the current series that closed with topical aqueous suppression, we observed a reduction in both the number and size of cystoid spaces in one case (Case 2; Table 2). However, it is unclear whether this was a consequence of closure of the FTMH itself or if dehydration of perifoveal cystoid changes resulted in successful closure. OCT images between the time therapy was initiated and closure of the MH was not available to demonstrate progressive decrease in the size of the cystoid spaces and associated improvement in the size or morphology of the MH. Cystoid edema was not present in Case 4 at presentation and therefore no change was observed. Alternative mechanisms of MH closure in Cases 2 and 4 include tractional forces from the ERM and release of vitreomacular adhesion, respectively. However, both the ERM and partial PVD in these cases appeared stable both on clinical examination and OCT between the development and closure of the MH.

In the two cases that failed to close without surgery, no improvement in cystoid changes was observed with topical dorzolamide-timolol. However, subsequent closure of the FTMHs with surgical intervention did result in decrease of perifoveal cystoid changes. The absence of perifoveal dehydration with topical therapy does not necessarily disprove the hydration theory. It is possible that topical aqueous suppression may not have been adequately effective in achieving cystoid dehydration.

This study has several limitations. The retrospective nature of the study may introduce bias in the selection of cases that were treated initially with medical therapy. The MHs in this series were small, which may have increased the likelihood of spontaneous closure. In fact, both cases that closed without surgery had very small MHs (< 200 μm). However, whether this can account for the six- to seven-fold increase from previously reported rates of spontaneous closures is unclear. Another limitation is the small number cases in this series. However, this is a pilot study to explore the idea of cystoid dehydration with topical aqueous suppression drops and not to demonstrate its efficacy conclusively.

In summary, we report a case series of four small FTMHs that were treated with topical aqueous suppression leading to closure in two out of four eyes without surgical intervention. A reduction in cystoid changes was observed in one of the two cases. A trial of medical therapy for a short duration did not lead to worse outcome or non-closure of MHs in this series. Future studies will be necessary to determine whether topical aqueous suppression has a useful role in the management of small idiopathic MHs.

References

  1. Gass JD. Idiopathic senile macular hole: Its early stages and pathogenesis. 1988. Retina. 2003;23(6 Suppl):629–639.
  2. Tornambe PE. Macular hole genesis: The hydration theory. Retina. 2003;23(3):421–424. doi:10.1097/00006982-200306000-00028 [CrossRef]
  3. Gentile RC, Landa G, Pons ME, et al. Macular hole formation, progression, and surgical repair: Case series of serial optical coherence tomography and time lapse morphing video study. BMC Ophthalmol. 2010;10:24. doi:10.1186/1471-2415-10-24 [CrossRef]
  4. Bakthavatchalam M, Lai FHP, Rong SS, et al. Treatment of cystoid macular edema secondary to retinitis pigmentosa: A systematic review. Surv Ophthalmol. 2018;63(3):329–339. doi:10.1016/j.survophthal.2017.09.009 [CrossRef]
  5. Grover S, Fishman GA, Fiscella RG, Adelman AE. Efficacy of dorzolamide hydrochloride in the management of chronic cystoid macular edema in patients with retinitis pigmentosa. Retina. 1997;17(3):222–231. doi:10.1097/00006982-199717030-00009 [CrossRef]
  6. Marmor MF, Maack T. Enhancement of retinal adhesion and subretinal fluid resorption by acetazolamide. Invest Ophthalmol Vis Sci. 1982;23(1):121–124.
  7. Sugiyama A, Imasawa M, Chiba T, Iijima H. Reappraisal of spontaneous closure rate of idiopathic full-thickness macular holes. Open Ophthalmol J. 2012;6:73–74. doi:10.2174/1874364101206010073 [CrossRef]
  8. Yuzawa M, Watanabe A, Takahashi Y, Matsui M. Observation of idiopathic full-thickness macular holes. Follow-up observation. Arch Ophthalmol. 1994;112(8):1051–1056. doi:10.1001/archopht.1994.01090200057022 [CrossRef]

Clinical Characteristics of Patients/Eyes Receiving Dorzolamide-Timolol for a Full Thickness Macular Hole

CaseAgeDuration of Topical Therapy (Days)Spontaneous ClosureFollow-Up (Months)Initial Visual AcuityFinal Visual AcuityLens StatusPosterior Vitreous Detachment
18235No1520/20020/200Pseudophakic+
27028Yes2020/20020/50Pseudophakics/p PPV
35521No1520/20020/25Phakic+
46328Yes620/6020/40PhakicPartial

Optical Coherence Tomography Characteristics of Eyes Receiving Dorzolamide-Timolol for a Full-Thickness Macular Hole

CaseHole Diameter (µm)Cystoid ChangesCystoid Spaces (Pre-Treatment)Cystoid Spaces (Post-Treatment)Largest Cystoid Diameter (Pre-Treatment)Largest Cystoid Diameter (Post-Treatment)Choroidal Thickness (Pre-Treatment)Choroidal Thickness (Post-Treatment)
1278+58154194197191
2136+13220033227214
3227+101218598185174
46400225199
Authors

From Mid Atlantic Retina, Wills Eye Hospital, Philadelphia.

Dr. Hsu has received grants from Roche/Genentech (San Francisco, CA) and Santen (Osaka, Japan), as well as grants and personal fees from Ophthotech (New York, NY), outside the submitted work. The remaining authors report no relevant financial disclosures.

Address correspondence to Jason Hsu, MD; Retina Service, Wills Eye Hospital, Suite 1020, 840 Walnut Street, Philadelphia, PA 19107; email: jhsu@midatlanticretina.com.

Received: January 31, 2018
Accepted: May 03, 2018

10.3928/23258160-20190129-17

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