Full thickness macular hole with subfoveal pigment epithelial detachment in chronic central serous chorioretinopathy: A therapeutic challenge

Abstract

We describe the diagnostic and therapeutic strategies employed in the management of a patient with subfoveal pigment epithelial detachments (PEDs) combined with full-thickness macular hole (FTMH) and discuss the possible pathophysiology of these diseases occurring concurrently. A 38-year-old patient with a history of central serous chorioretinopathy (CSC) presented with FTMH overlying a large subfoveal serous PED. Multimodal imaging confirmed the same and intravitreal anti-vascular endothelial growth factor (VEGF) injections and eplerenone failed to resolve the PED. Spontaneous resolution of the large PED was observed later and pars plana vitrectomy with internal limiting membrane peeling closed the macular hole successfully. However, the PED with fibrinous CSC recurred postoperatively and low fluence photodynamic therapy (PDT) was done to tackle the same. At 10 months’ follow-up, the final vision was 6/9, the macular hole remained closed, and the PED had not recurred. Macular hole formation may be the result of choroidal hyperpermeability and leakage in the backdrop of CSC which gives rise to an exudative component causing mechanical stretching and disruption of the overlying sensory retina. Spontaneous uncomplicated resolution of large subfoveal PED in CSCR is rare. This case was managed with a combination of intravitreal anti-VEGF injections, surgery, and PDT. The therapeutic challenge here was the timing of surgery.

Introduction

Pigment epithelial detachments (PED) are the hallmark of a wide spectrum of diseases that affect the macula like central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), age-related macular degeneration (AMD), retinal angiomatous proliferation, and at times in conjunction with multiple systemic diseases. PEDs are reported to occur in 10.5% of all CSC[1] and constitute an independent risk factor for poor visual outcome.[1] In cases of PEDs associated with CSC, the most frequent outcome is a resolution with retinal pigment epithelium (RPE) atrophy. Symptomatic subfoveal serous PEDs necessitate fundus fluorescein angiography (FFA) or ICGA-guided photodynamic therapy (PDT) with verteporfin[2] which is believed to incite hypoperfusion of choriocapillaries and bring about choroidal vascular remodeling negating choroidal congestion, hyperpermeability, and extravascular leak.[2]

A full-thickness macular hole (FTMH) owes its etiopathogenesis to a multitude of factors like tangential and anteroposterior traction at the vitreomacular interface and although spontaneous closure has been observed in smaller sized idiopathic holes, surgical intervention with a pars plana vitrectomy (PPV) with intravitreal gas injection is the norm.

We report an unusual case of chronic CSCR with massive foveal serous PED associated with FTMH and its successful management.

Case Report

A 38-year-old Asian male, who was a known case of chronic CSC presented initially in 2014 with a best-corrected visual acuity (BCVA) of 6/6 in the right eye (RE) and 6/36 in the left eye (LE). Fundus biomicroscopy of LE showed RPE degeneration and foveal thinning following chronic CSC and RE showed a lamellar macular hole (LMH) with multiple PEDs. Spectral-domain optical coherence tomography (SD-OCT) in LE showed foveal thinning and RPE degeneration, RE showed LMH with multiple small serous extrafoveal PED inferotemporally [Figure 1]. Since the FFA revealed no leakage, he was managed conservatively. Two years after the initial presentation, he reported sudden deterioration of vision in the RE for 3 weeks. On examination, BCVA was 6/12 in his RE and 6/36 in his LE. The anterior segment examination and intraocular pressure were normal in both eyes. Dilated fundus examination of the LE showed the same clinical picture as previous, but the RE showed a FTMH over a large subfoveal PED [Figure 2i]. A subsequent SD-OCT showed a massive subfoveal serous PED with an overlying FTMH with cystic changes at the edges [Figure 2ii]. FFA showed window defect in the foveal center corresponding to the macular hole and leakage from PED in late phases with pooling of dye [Figure 2iii]. Multiple extra-macular serous PEDs and RPE window defects were present suggestive of CSCR. Considering the size of subfoveal PED, the patient was started on oral Eplerenone 50 mg OD. However, no objective clinical improvement was observed after 3 months of therapy [Figure 3a]. FFA along with Indocyanine green angiography was done at this point, which revealed hyperfluorescence within PED on the nasal side of the fovea, raising suspicion of a vascularized PED [Figure 3b]. However, the OCT was not indicative of any breach in the RPE or Bruch’s membrane. The patient then underwent monthly injections of intravitreal bevacizumab (Avastin 1.25 mg/0.05 ml) thrice but failed to manifest any structural or functional improvement [Figure 4a]. Consequently, he was advised PDT but failed to comply with further treatment. After 3 months, he presented with spontaneous improvement in vision of RE to 6/9. OCT showed complete resolution of the subfoveal PED, leaving behind the macular hole and intact RPE [Figure 4b]. He then underwent PPV with Internal Limiting Membrane Peeling (ILMP) and C3F8 (16%) gas tamponade. 1 month postoperatively, the hole had closed with no evidence of PED or SRF [Figure 4c]. On serial follow-up at 4 months, the vision had dropped again to 6/12. SD-OCT showed a massive subfoveal PED with subretinal fluid (SRF) and thick fibrinous exudation but the macular hole remained closed [Figure 4d]. On FFA, there was a late leakage in atypical smoke stack pattern and leakage from the PED suggestive of active CSC [Figure 5]. A low fluence PDT was done, giving 2 spots with power 300 mW/cm, spot size 5500 microns, and duration 83 s. In a fortunate turn of events, the PED resolved at 2 months with no residual SRF and closed macular hole and it was maintained so at his follow-up visit 10 months post-PDT, with a final vision of 6/9 [Figure 4e].

Figure 1.

SD-OCT horizontal line scan of RE shows (a) LMH (blue arrow) with extrafoveal multiple small serous PED (b) (blue arrowhead), LE showed foveal thinning and RPE degeneration (c) (yellow arrow). SD-OCT: Spectral-domain optical coherence tomography, LMH: Lamellar macular hole, RE: Right eye, LE: Left eye, PED: Pigment epithelial detachment

Figure 2.

(i) Colour fundus photograph of RE (A) shows full thickness macular hole (blue arrow) with large subfoveal PED (blue arrowhead). LE (B) shows RPE degeneration (yellow arrow) and foveal thinning (yellow arrowhead) (ii) RE Spectral-domain optical coherence tomography horizontal line scan passing through the foveal centre (A) and juxtafoveal inferior section (B) shows the presence of FTMH over a massive subfoveal serous PED and subretinal fluid. (iii) Fluorescein angiography shows (A) window defect in the foveal centre corresponding to macular hole (blue arrow) and (B) multiple extramacular PEDs (blue triangle) and RPE window defects suggestive of CSC. (C) Leakage from PED (blue star) in late phases with pooling of dye. RE: Right eye, PED: Pigment epithelial detachment, LE: Left eye, RPE: Retinal pigment epithelium, PED: Pigment epithelial detachment, FTMH: Full-thickness macular hole

Figure 3.

(a) Spectral-domain optical coherence tomography after 3 months of eplenerone therapy, shows no change with persistent large subfoveal PED and subretinal fluid FFA with ICGA reveals a suspicious hot-spot (blue arrow) within PED on the nasal side of fovea, from early(b) mid (c) and (d) late phases raising suspicion of a vascularized PED

Figure 4.

(a) Spectral-domain optical coherence tomography horizontal line scan passing through the foveal center shows no clinical improvement Post intravitreal Bevacizumab (Avastin) (b) Spectral-domain optical coherence tomography horizontal line scan passing through the foveal centre shows the presence of FTMH and spontaneously resolved PED (c) SD-OCT shows closed macular hole and minimal subretinal fluid. Pachyvessels and choriocapillary attenuation with thick underlying choroid is also noted. (d) SD-OCT 4 months post operatively shows the presence subretinal fluid, thick fibrinous exudation and large subfoveal PED with a closed macular hole (e) Post-PDT 1 month, SD-OCT showed almost (i) complete resolution of CSC, with mild residual subretinal fluid (blue arrowhead). At 7 months follow up, (ii) OCT showed complete resolution with closed macular hole with no subretinal fluid or PED. FTMH: Full-thickness macular hole, PED: Pigment epithelial detachment, SD-OCT: Spectral-domain optical coherence tomography, PDT: Photodynamic therapy, CSC: Central serous chorioretinopathy

Figure 5.

FFA and ICGA of right eye shows the presence of early hyperfluorescence, (a) increasing in intensity through mid (b) and late phase, (c) suggestive of atypical smoke stack leak (blue arrow) from the nasal edge of the PED and late pooling of dye in CSC. Multiple extrafoveal PEDs, dilated choroidal vessels (blue arrowhead) and areas of choroidal hyperpermeability are also noted. FFA: Fundus fluorescein angiography, PED: Pigment epithelial detachment, CSC: Central serous chorioretinopathy

Discussion

We report a case of FTMH formation in the setting of a leaking subfoveal PED in CSCR. This discussion aims to explore the possible pathophysiology of hole formation and the sequence of treatment modalities to be followed in such cases. The spontaneous resolution of a massive subfoveal PED, as in our case, is extremely rare as they frequently result in RPE rip.

The pathogenesis of macular hole has conventionally been attributed to antero-posterior and tangential vitreous traction, but the role of intra-foveal splitting and central dehiscence[3] must be reiterated at this point. In MH with concomitant PEDs, stretching of the neurosensory retina by the expanding PED and focal traction by contracting CNVMs, either as part of the natural evolution of the primary disease or as a response to anti-vascular endothelial growth factors (VEGFs), may be considered as the causative factor for hole formation. Panthier et al.[4] reported a case of FTMH with PED appearing in a case of AMD and had attributed the MH formation to the progressive resorption of drusenoid debris and the subsequent shearing forces from RPE retraction causing the overlying tissue to tear. The development of a hole atop the PED suggests that expansion of the volume of the PED results in internal pressure build-up, stretching, and rupture of the neurosensory retina. Hence, we presume that these two conditions occurring simultaneously would be due to increased choroidal hydrostatic pressure in the backdrop of CSCR resulting in an enlarging PED with exudative SRF. Consequently, there is stretching of the overlying thin retina and when coupled with centrifugal stretching forces from underneath the RPE, culminates in a FTMH.

FTMH occurring in conjunction with PED poses a therapeutic dilemma. The first such reported case was by Imasawa[5] in a patient with PCV. That patient was treated with PDT which collapsed the PED followed by a subsequent PPV which led to the complete closure of the macular hole. A similar approach was successful in a case reported by Recchia and Williams[6] in a smaller MH. Raiji et al.[7] reported a patient of neovascular AMD in whom treatment of a leaking PED with intravitreal ranibizumab culminated in a macular hole. This patient underwent PPV with intravitreal gas tamponade which achieved hole closure but the PED remained unchanged and postoperative sessions of PDT also failed to show any response. Inoue[8] also reported the two cases of macular hole appearing in conjunction with PCV. In the first case, anti-VEGF injections and PDT led to the collapse of the PED, and thereafter, a PPV was done which succeeded in closing the FTMH, with marked visual improvement. However, in the second case, anti-VEGF injections and PDT failed to demonstrate any response, and PPV following that also failed to restore the structural integrity of the macula. There has been a reported case resolution of a macular hole associated with PED with anti-VEGF injections alone.[9] Sethia et al. have reported spontaneous macular hole formation and subsequent resolution with anti-VEGF injections in a case of PCV.[10]

In our case, we had administered a trial of oral eplerenone and intravitreal bevacizumab injections with the intent of collapsing the subfoveal serous PED, but to no avail. In the next visit, since spontaneous regression of PED was observed, the objective was to surgically close the FTMH. We dealt with the subsequent recurrence of fibrinous CSCR with PED with a session of PDT. However, in the case reported by Imasawa, the vision remained the same as before treatment, as opposed to our case in which the patient had significant visual recovery despite the initial larger basal diameter of the FTMH. It needs to be reiterated, however, that PCV eyes as mentioned by them, are often subjected to recurrent PEDs, degradation of RPE and neurosensory retina that leads to a poorer visual outcome generally. Of the cases reported by Inoue, which were treated with intravitreal anti-VEGFs, PDT and PPV, the first case responded and had a satisfactory final vision. However, the second case, as well as the case reported by Raiji et al. had negligible improvement. They proposed that the persistent posterior elevation or stretching forces resulting from the PED contributed to the failure of the vitrectomy to close the FTMH. The visual recovery in our case has been good despite the recurrence of PED, preexisting chronic CSCR, and the macular hole.

Various permutations and combinations of therapeutic strategies comprising of anti-VEGFs, PDT and surgery were tried by different authors as evidenced in their reports. PDT had successfully collapsed the PED for Imasawa but was found to be ineffective in cases reported by Raiji and Yannuzzi. The vitrectomy thereafter had provided anatomical closure of MH for only the former authors. Raiji et al.[7] claimed that the presence of a subfoveal PED should not preclude any attempts to surgically close the MH. We believe that the primary aim must be to treat PED and that the PPV should essentially follow that to eliminate possible stretching forces from within the PED that caused the MH to form initially and to prevent the recurrence. In addition, in this case, the chronic CSCR may have created a degenerated RPE and thinned out retina which was unlikely to withstand further stretching from PEDs. The sliding of retinal tissue, which is the usual healing mechanism that follows surgical repair of macular hole, might not be effective on an inflected RPE surface overlying the massive PED. Furthermore, surgical peeling of the ILM over a massive convex subfoveal PED runs the risk of RPE rip due to mechanical shearing forces. Hence, we treated the CSCR first to flatten the PED, followed by surgery for the successful macular hole closure.

In summary, chronic CSCR with large foveal PED associated with FTMH is unreported to date and the variety of therapeutic modalities that can be tried along with their timing is the managerial challenge for a successful outcome.

Consent for publication

The patient gave written permission for the presentation of clinical details and images in this study.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.