Pneumatic Displacement with Intravitreal Plasminogen Activator (PA) versus Vitrectomy with Subretinal PA for Submacular Haemorrhage

Research Article

Austin J Clin Ophthalmol. 2019; 6(1): 1099.

Pneumatic Displacement with Intravitreal Plasminogen Activator (PA) versus Vitrectomy with Subretinal PA for Submacular Haemorrhage

Ching J1,4†, Cardoso J2†, Cabrera RG2, Grabowska A2, Karia N2, Saidkasimova S1‡* and Chandra A2,3‡*

¹Norfolk and Norwich University Hospitals, Colney Lane, Norwich, NR4 7UJ, UK

²Southend University Hospital, Prittlewell Chase, Essex, SS0 0RY, UK

³Vision and Eye Research Unit, Anglia Ruskin University, Cambridge, UK

4John Van Geest Centre for Brain Repair, E.D. Adrian Building, Cambridge, CB2 0PY, UK †Authors contributed equally ‡Authors contributed equally

*Corresponding author: Mr Aman Chandra, Department of Ophthalmology, Southend University Hospital, Prittlewell Chase, Southend on Sea, SS00RY, Essex, Vision and Eye Research Unit, Anglia Ruskin University, Cambridge, United Kingdom

Mr Aman Chandra, Department of Ophthalmology, Southend University Hospital, Prittlewell Chase, Southend on Sea, SS00RY, Essex, Vision and Eye Research Unit, Anglia Ruskin University, Cambridge, United Kingdom

Received: December 05, 2018; Accepted: January 23, 2019; Published: January 30, 2019


Introduction: To compare the efficacy of pneumatic displacement with intravitreal recombinant tissue plasminogen activator (rTPA) [Group 1] versus vitrectomy with subretinal injection of rTPA with/without anti-VEGF [Group 2] for submacular haemorrhage (SMH) in patients with neovascular age-related macular degeneration (nAMD) in two tertiary referral centres.

Methods: Retrospective analysis of thirty consecutive patients presenting with SMH and treated with the aforementioned regimens in two surgical units between 2012 to 2016. Primary outcome measure was SMH displacement. Secondary outcomes included best-corrected visual acuity (BCVA) change post-operatively, SMH height, SMH area, and surgical complications. Optical coherence tomography (OCT) images and clinical data used to analyse outcomes.

Results: Eleven patients included in Group 1 and 19 in Group 2. Haemorrhagic displacement was complete in 9 (82.8%) out of 11 and 18 (94.7%) out of 19 patients in Groups 1 and 2, demonstrating no difference between them (p=0.536). BCVA improved by -0.50±0.74 (p=0.045) and -0.72±0.93 (p=0.004) compared to baseline at 6 months in Groups 1 and 2, with no difference between groups (p=0.155). Subfoveal haemorrhage height reduced (Group 1:- 900.57μm, p=0.007; Group 2:-607.27μm, p<0.001), without difference between groups (p=0.582). SMH area reduced significantly in Group 2 but not 1 (Group 1:-44.18μm, p=0.078; Group 2:-30.28μm, p<0.001), without difference between groups (p=0.913).

Conclusion: Intravitreal treatment and vitrectomy were equally effective at subfoveal haemorrhagic displacement. BCVA gains did not differ significantly between techniques. OCT data demonstrated similar efficacy in both techniques. This data supports the use of either intravitreal or vitrectomy treatment as a first line therapy for SMH.

Keywords: Subretinal haemorrhage; Neovascular age-related macular degeneration; Anti-vascular endothelial growth factor; Tissue plasminogen activator; Pneumatic displacement; Gas


The natural history of submacular haemorrhage (SMH) portends a poor visual prognosis and is often associated with neovascular age related macular degeneration (nAMD), though many aetiologies exist [1-3]. The Submacular Surgery Trial demonstrated that physical removal of blood through a posterior pole retinotomy did not improve best corrected visual acuity (BCVA) [4]. Several mechanisms for retinal toxicity secondary to SMH have been proposed, where animal experiments have shown a barrier effect by fibrin infiltration created by SMH prevents choroidal perfusion of the neurosensory retinal layers [5-7]. Further mechanisms include direct toxic effect on photoreceptor function from haemolytic products iron and hemosiderin [8-11].

As a result, a number of treatment strategies to overcome SMH have been proposed, including anti-vascular endothelial growth factor (VEGF) intravitreal injections alone or in combination with techniques to mechanically displace the SMH [12-15]. Pneumatic displacement of submacular haemorrhage with expansile gas was first introduced in 1996 and has subsequently been shown to result in visual gains over the natural history of SMH [A,16,17]. Thereafter, attempts to improve efficacy by combining intravitreal expansile gas with intravitreal rTPA have been shown to result in complete haemo-displacement in 73% of patients (n = 192) [16]. Hillenkamp and colleagues went on to demonstrate in 47 patients that subretinal rTPA with vitrectomy was more effective than intravitreal rTPA, thus paving the way for development of a variety of surgical regimens that include subretinal anti-VEGF [8,18,19].

In the present study, we sought to compare two groups of patients that underwent less invasive intravitreal treatment and more invasive vitrectomy assisted haemodisplacement techniques for SMH as a complication of nAMD. Each technique has been shown to have efficacy in a number of independent studies [16,19]. Recent comparative studies have not shown either of these techniques to be superior in haemodisplacement or visual outcome [20-22].

Herein we present a retrospective non-randomised comparative case series of consecutive patients treated with pneumatic displacement versus vitrectomy assisted displacement in two centres serving a similar geographic area.

Methods and Materials

All patients with SMH secondary to nAMD treated in two centres from 2012 to 2016 were retrospectively recruited to the study. Inclusion criteria were: fovea involving SMH with sudden onset of reduced vision worse than 6/36; area at least two disc diameters and duration no more than 45 days in group 1 and no more than 14 days in Group 2. Exclusion criteria were pre-existing comorbidity including underlying extensive subretinal fibrosis/ geographic atrophy and SMH caused by pathologies other than nAMD. This study adhered to the tenets of Declaration of Helsinki. Full consent was obtained as standard from every patient prior to proceeding to surgery.

Patients were divided into two groups: Group 1 received intravitreal pneumatic displacement (sulfahexafluoride [SF6] or hexafluoroethane [C2F6] gas) and intravitreal rTPA with/without intravitreal anti-VEGF and Group 2 received pars plana vitrectomy in combination with subretinal rTPA, with/without subretinal Anti- VEGF, with SF6 gas tamponade.

The main outcome measure was haemo-displacement. This was defined as complete if all foveal blood was displaced, partial if some blood remained in the sub foveal region and incomplete if blood remained at the fovea, at 1 months review, as described elsewhere [19]. Secondary outcomes included BCVA, the number of pre- and post-operative anti-VEGF injections, SMH height, SMH area and surgical complications.

Patient assessment pre- and post-operatively included Snellen best corrected visual acuity, macular optical coherence tomography (Topcon OCT-2000, Topcon Corporation, Tokyo, Japan; RTVue-100 FD-OCT, Optovue Inc. Fremont, CA, USA; HRA Spectralis, Heidelberg Engineering, Heidelberg, Germany), tonometry, anterior segment and dilated fundus slit lamp examination. Co-morbidities and regular medication was recorded for each patient.

For analysis, BCVA was converted to logarithm of minimum angle of resolution (LogMAR) values [23]. OCT images were analysed by taking the Central Retinal Thickness and Average Retinal Volumes calculated by the Topcon OCT mk. III, the RTVue-100 and Heidelberg Engineering HRA Spectralis softwares. SMH height was measured from the base of the haemorrhage to the first photoreceptor layer at the fovea and at the maximum height of the haemorrhage. The area of SMH was outlined using the analysis function on the Topcon imaging system as described previously and applied to the Heidelberg Spectralis and RTVue-100 area measurement function [18].

Surgical technique

Group 1: Pneumatic displacement was performed with intravitreal injection of 50mcg/0.1ml of rTPA (Actilyse® Boehringer, Ingelheim) diluted to above concentration) and an intravitreal injection of an undiluted expansile concentration of SF6 (0.5ml) or C2F6 (0.3ml) according to surgeon preference. In some patients, an intravitreal injection of 1.25mg/0.05ml of Bevacizumab (Avastin, Genetech, San Francisco, USA) was used after the intravitreal rTPA, according to surgeon preference. Patients were postured supine for 30 minutes followed by face down posture for 3 days. Patients were reviewed at day one, when a decision regarding further intervention (pars plana vitrectomy assisted displacement) was taken. They were then reviewed at 2 weeks, and subsequently every 4-6 weeks according to the anti VEGF treatment regime.

Group 2: All patients underwent 23 gauge three port vitrectomy under local anaesthetic as a day case. After core and peripheral vitrectomy 0.05ml of ranibizumab (Lucentis) and 0.05ml of 25mcg/ml rTPA (Actilyse® Boehringer, Ingelheim) diluted to above concentration in hospital pharmacy) and 0.05ml of ranibizumab (Lucentis) (if patient met local Clinical Commissioning Group criteria) was injected into the subretinal space using 41 gauge cannula (DORG). Injection site selected at the highest point of SMH taking into account desirable direction of displacement of haemolysed blood away from fovea. Care was taken to inject slowly to avoid over inflation and break through the fovea”. Fluid-air exchange with 22% SF6 gas injection was carried out at the end of procedure. Patients were postured supine for an hour followed by upright or on their temporal side posture depending on the direction of intended displacement of SMH for 3 days.

Patients were reviewed at 2 weeks, post-operatively and every 4-6 weeks thereafter. All patients received on going treatment with intravitreal anti-VEGF.


Appropriate descriptive and comparative statistical analysis was undertaken using GraphPad Prism 7, GraphPad Software Inc., California, for Mac. Statistical significance was considered a p value of <0.05.


Thirty patients were included in the study. Fourteen and 16 patients were treated at the SUH and NNUH, respectively. Eleven patients were allocated to Group1 and 19 to Group 2. Patient baseline characteristics are summarised in Table 1.

Citation: Ching J, Cardoso J, Cabrera RG, Grabowska A, Karia N, Saidkasimova S, et al. Pneumatic Displacement with Intravitreal Plasminogen Activator (PA) versus Vitrectomy with Subretinal PA for Submacular Haemorrhage. Austin J Clin Ophthalmol. 2019; 6(1): 1099.