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Journal Français d'Ophtalmologie
Volume 39, n° 8
pages 661-667 (octobre 2016)
Doi : 10.1016/j.jfo.2016.05.010
Received : 7 January 2016 ;  accepted : 27 May 2016
Follow-up after surgery for hemorrhagic AMD
Rôle du suivi dans la prise en charge des patients opérés d’hématome maculaire compliquant une DMLA exsudative
 

D. Garcia a, b, L. Mahieu b, G. Soubrane c, L. Salmon b, A. Renouvin b, V. Pagot-Mathis b, F. Matonti d, V. Soler b, e,
a Ophthalmology department, centre hospitalier de Bigorre, boulevard Maréchal-de-Lattre-de-Tassigny, 65000 Tarbes, France 
b Retina unit, ophthalmology department, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Docteur-Baylac, TSA 40031, 31059 Toulouse cedex 9, France 
c Hôtel-Dieu hospital, 75004 Paris, France 
d Hôpital Nord, chemin des Bourrely, 13915 Marseille, France 
e Laboratoire GR2DE, centre de physiopathologie de Toulouse Purpan (CPTP), place du Docteur-Baylac, TSA 40031, 31059 Toulouse cedex 9, France 

Corresponding author. Retina unit, ophthalmology department, hôpital Pierre-Paul-Riquet, CHU de Toulouse, place du Docteur-Baylac, TSA 40031, 31059 Toulouse cedex 9, France.
Summary
Introduction

The long-term functional results of macular hematoma (MH) surgery in exudative AMD are often limited. The goal of this study was to compare visual outcomes of monthly versus bimestrial follow-up in these patients.

Methods

Retrospective, interventional case series. Population : 21 eyes of 21 patients with SMH associated with exudative AMD. Inclusion criteria: first SMH associated with exudative AMD, with 1-year postoperative follow-up. Exclusion criteria: blood located exclusively underneath the retinal pigment epithelium on OCT imaging, SMH due to different etiology, lost to follow-up, ≤5 postoperative visits and a different surgical protocol as described. Patients were divided into two groups according to the number of postoperative visits (number of intravitreal injections [IVT] combined with the number of consultations, only one visit was recorded when IVT and consultation occurred on the same day) during the 1-year postoperative follow-up: group 1 had ≥11 visits (n =8); group 2 had 6 to 10 visits (n =13). All eyes underwent vitrectomy with subretinal injection of recombinant tissue plasminogen activator, fluid-gas exchange and anti-VEGF intravitreal injection. The main outcome was change in best-corrected visual acuity (BCVA).

Results

Considering visual acuity (VA) change between 1-month and 1-year postoperative follow-up examinations, group 1 had statistically significant greater VA changes (logMAR −0.29±0.44 vs logMAR 0.42±0.73; P =0.016; P =0.016). In patients that had exudative recurrences (ER), group 1 received more anti-VEGF IVT than group 2 (P =0.045).

Conclusion

Our results showed that monthly follow-up, between the IVT series, is highly recommended to preserve postoperative VA in patients undergoing surgery for SMH associated with AMD.

The full text of this article is available in PDF format.
Résumé
Introduction

Les résultats fonctionnels de chirurgie d’hématomes maculaires compliquant une DMLA exsudative (HM) sont souvent limités à long terme. Le but de cette étude était, chez les patients opérés d’HM, de comparer l’évolution fonctionnelle des patients avec suivi postopératoire mensuel versus ceux avec suivi au moins bimestriel.

Matériel et méthodes

Série rétrospective ; 21 yeux. Critères d’inclusion : premier HM, suivi postopératoire d’un an ; critères d’exclusion : HM d’étiologie autre que DMLA exsudative, localisation exclusivement sous-épithéliale de l’hématome, ≤5 visites postopératoires. Deux groupes de patients définis selon le nombre N de visites postopératoires (addition du nombre d’injections intravitréennes [IVT] et de consultations, une seule visite étant comptée en cas d’IVT et de consultation le même jour), sur un an : groupe 1 avec N11 visites (n =8 patients) ; groupe 2 avec 6N10 (n =13). Tous les patients ont bénéficié d’une vitrectomie avec injection sous-rétinienne d’activateur tissulaire du plasminogène recombinant, tamponnement par gaz et IVT d’anti-VEGF. Critère de jugement principal : évolution de la meilleure acuité visuelle corrigée (MAVC) entre les visites à 1 mois et 1 an postopératoires.

Résultats

L’évolution de la MAVC entre les visites postopératoires à 1 mois et 1 an était significativement meilleure dans le groupe 1 (logMAR −0,29±0,44 vs logMAR 0,42±0,73 ; p= 0,016). Dans les sous-groupes de patients ayant présenté des récurrences exsudatives, les patients du sous-groupe 1 avaient reçu plus d’IVT (p =0,045).

Conclusion

Chez les patients opérés d’HM compliquant une DMLA exsudative, un suivi mensuel entre les séries d’IVT est recommandé pour préserver la MAVC postopératoire.

The full text of this article is available in PDF format.

Keywords : Anti-VEGF, Follow-up, Intravitreal injection, Tissue plasminogen activator, Vitrectomy, Wet macular degeneration

Mots clés : Anti-VEGF, Suivi, Injection intravitréenne, Activateur tissulaire du plasminogène, Vitrectomie, DMLA exsudative


Introduction

The management of exudative age-related macular degeneration (AMD) has been improved by antivascular endothelial growth factor (VEGF) therapies [1, 2].

However, submacular hemorrhage (SMH) associated with AMD remains a severe complication associated with poor visual prognosis [3, 4], mainly due to blood toxicity on the photoreceptors and the SMH mechanical effect [5, 6, 7].

Several surgical procedures for management of SMH have been developed. Some authors recommend observation after the first bleeding [3, 8, 9]; others use anti-VEGF intravitreal injections (IVT) as the sole therapy [10, 11, 12, 13, 14]. Surgical removal of blood and associated choroidal neovascularization (CNV) has not been shown to increase final visual acuity (VA) [15]. Several surgical procedures, associated or not, aiming at blood displacement rather than its removal have been developed to avoid subretinal manipulation: intravitreal gas with or without pars plana vitrectomy (PPV), subretinal or intravitreal use of recombinant tissue plasminogen activator (rtPA) and the subretinal injection of air [16, 17, 18, 19, 20]. Each procedure may be associated with anti-VEGF IVT [21]. PPV with rtPA subretinal injection and fluid-gas exchange has become the commonest surgical procedure, leading to SMH successful displacement and significant short-term vision improvement [17, 19, 20, 22, 23, 24]. However, the long-term effectiveness of this technique not been extensively evaluated [25].

This retrospective study was designed to understand the effect of a monthly follow-up vs. an “at least” bimestrial follow-up on VA evolution 1 year postoperatively after PPV with subretinal injection of rtPA, fluid-gas exchange and anti-VEGF IVT for AMD-associated SMH.

Methods

In this retrospective, interventional, single center study, we reviewed the medical records of all patients who underwent surgery for SMH between November 2011 and April 2014 at the Retina unit, ophthalmology department, hôpital Pierre-Paul-Riquet (CHU de Toulouse, Toulouse, France).

The inclusion criteria was the first occurrence of retrofoveal SMH due to the subretinal bleeding secondary to exudative AMD, with a postoperative follow-up of at least 1 year in our center or with a referring ophthalmologist. Patients were excluded if the blood extended exclusively underneath the pigment epithelium and if no blood was located underneath the retina on OCT imaging, if the SMH was due to a different etiology (such as trauma, macroanevrysm, myopia and polypoidal choroidal vasculopathy), if follow-up was less than 49 weeks after surgery, if patients had five or less postoperative examinations (we considered they demonstrated a follow-up that was under-optimized and out of good practice recommended by the French Health High Authority) or if patients did not undergo the surgical protocol described. The fovea was defined as a 1.5-mm diameter circular area (approximately one disc diameter centered on the foveola) [25].

Three surgeons (L.M., V.P.M., V.S.) performed the operations. The surgical indication was SMH underneath the fovea with hemorrhage thickness greater than 200 microns and a surface of more than one disc diameter (to perform subretinal injection without any risk of foveolar injury). Surgery was performed before day 7 following SMH occurrence. The procedure consisted of 23- or 25-G PPV. Following the procedure, 0.1mL of rtPA solution (0.25mg/mL) was injected in the subretinal space through a 41-G cannula. A fluid-air exchange, followed by an air-SF6-20% gas tamponade and a 0.05-mL ranibizumab IVT were then performed. Finally, the patient had to maintain a prone position for 1hour four times a day, over 5 days. Successful displacement of the hemorrhage was obtained when the central 1000μm area was free of blood. In the case of SMH recurrence, patients underwent a second surgical procedure.

For each patient, the following data were collected: age, gender, ophthalmologic and general history, treatments, number of IVT before SMH occurrence in the studied eye, preoperative and postoperative best-corrected visual acuities (BCVA), time between SMH occurrence and surgery, quality of the subretinal blood displacement after surgery and any complications during surgery. Other data collected were preoperative and postoperative fluorescein angiography aspects, and SD-OCT (Spectralis, Heidelberg Engineering, Heidelberg Deutschland) features. SMH thicknesses were measured with SD-OCT by evaluating the retrofoveal distance between the retinal pigment epithelium and ellipsoid layer.

BCVA were converted into logMAR for statistical analysis. Visual acuity of “hand motion” was equal to logMAR 2.3 and “light perception” to logMAR 3.0. The VA of both eyes before SMH occurrence were recorded, at diagnosis and 1 month±1 week, 6 months±2 weeks, and 1 year±3 weeks after surgery. Improvement in VA was defined as a difference of −0.2 logMAR or less between the two examinations, whereas decreased VA was a difference of +0.2 logMAR or greater.

The numbers of postoperative follow-up examinations and postoperative anti-VEGF IVT were recorded. Indications of these IVT were exudative recurrences for which diagnosis was ascertained using the fundus or fluorescein angiography or SD-OCT findings. Exudative recurrences were diagnosed with the following features: hemorrhages during fundus examination, a new leakage during fluorescein angiography, or the presence of subretinal fluid or 100 micron increase of central retinal thickness on OCT examinations.

The numbers of postoperative follow-up examinations and postoperative IVT were used to assess the number of postoperative visits. Only one visit was recorded when IVT and consultation occurred on the same day. If the patient was not followed by our center but by his ophthalmic practitioner, all the clinical and imaging data was obtained.

The patients were divided into two groups: group 1 was defined as ≥11 visits after surgery and group 2 had attended 6 to 10 visits. Visual acuity between the two groups was compared at 1 month, 6 months and 12 months during the postoperative follow-up examinations. We also compared changes of the BCVA from baseline (1 month postoperative examination) to 6 and 12 months postoperatively between the two groups.

For statistical analysis, a P -value of 0.05 was set for a type I error. The Mann-Whitney test was used to analyze the change in VA during this 1-year follow-up in each group. Fisher's exact test was used to make statistical comparisons of proportions.

Results
Clinical data

During the inclusion period, 28 patients underwent surgery. Seven patients that had less than 6 visits (insufficient follow-up) were excluded. Eight patients were included in group 1 (≥11 postoperative visits) and 13 in group 2 (number of postoperative visits was between 6 and 10). There was no significant difference between the preoperative characteristics of the two groups (Table 1). The mean age was 83±7.9 years. Concerning the etiology of SMH, a retinal pigment epithelium tear secondary to AMD was observed in four patients in group 1 and six in group 2 (P =1). There were 13 AMD-affected contralateral eyes (six in group 1 vs. seven in group 2; P =.4). One contralateral eye in group 2 had SMH several years previously.

Surgery

The mean time to surgery was 3.1±1.7 days (3.4±1.6 days in group 1; 3±1.8 days in group 2; P =0.6). A successful displacement of the hemorrhage was obtained in five patients (62.5%) of group 1 and nine (69%) of group 2 (P= 1). We observed post-vitrectomy complications in three patients from group 1 (37.5%) and in seven from group 2 (53.8%) (P =0.659). These complications were: vitreous hemorrhages associated with or without hyphema (two in group 1 and four in group 2); isolated hyphema (one in group 1 and two in group 2); and one macular hole in group 2. Among the nine patients with hemorrhagic complications, four were administered a blood-thinning treatment: one in group 1 had an anticoagulant drug while, in group 2, one received an antiplatelet drug, one an anticoagulant drug and one had both treatments (P =0.540).

Characteristics of visual acuity of the SMH-affected eye at the follow-up examinations

The mean VA values during the follow-up period are given in Table 2 and illustrated in Figure 1. The mean preoperative VA was logMAR 1.67±0.63 with no statistical difference between the two groups. The mean postoperative VA was at the 1-month postoperative follow-up examination, logMAR 1.53±0.84 and, at 1 year, logMAR 1.68±0.96 with no difference between the groups (P =0.49 and P =0.66, respectively). The mean postoperative VA at 1 month (logMAR 1.53±0.84) and 1 year (logMAR 1.68±0.96) were not significantly different from the preoperative values (P =0.44 and 0.97, respectively).



Figure 1


Figure 1. 

Mean visual acuity (logMAR) with standard deviation of group 1 (black; n =8) and group 2 (white; n =13) before surgery, and after surgery at 1 month, 6 months and 12 months follow-up examinations. Group 1 is defined by monthly postoperative follow-up visits in 1 year11. Group 2 is defined by bimestrial postoperative follow-up with the number of visits in 1 year between 6 and 10.

Zoom

Differential change in mean visual acuity

The change in mean VA between the preoperative examination and the examination at 1 month was logMAR −0.13±1 for all patients. The mean VA evolution between preoperative and postoperative 1-month follow-up examinations were logMAR −0.03±1.35 in group 1 and logMAR −0.21±0.76 in group 2 (P =0.83).

As described in Table 2 and in Figure 2, between the 1-month and 1-year follow-up examinations, we found a mean VA improvement in group 1 (logMAR −0.29±0.44) and a decrease in group 2 (logMAR 0.42±0.73); this difference was significant (P =0.016).



Figure 2


Figure 2. 

Evolution of mean visual acuity (logMAR), with trend lines, from 1 month after surgery to 1 year for all patients (dark grey dots), group 1 (black dots; n =8) and group 2 (light grey dots; n =13) patients. Group 1 is defined by monthly postoperative follow-up with the number of visits in 1 year11. Group 2 is defined by bimestrial postoperative follow-up with the number of postoperative visits in 1 year between 6 and 10. The asterisk symbol* indicates significant P -value (<0.05), with Mann-Whitney test, when comparing the results of groups 1 and 2.

Zoom

Number of visits

The mean number of visits was 11.5±0.5 in group 1 and 7.7±1.4 in group 2 (P =0.0001). There were more postoperative IVT of anti-VEGF in group 1 than in group 2 (respectively, 3.1±2.2 and 1.6±1.9; P =0.164). The mean number of consultations between the IVT (without scheduling IVT afterwards) was 8.4±2.2 in group 1 and 6.1±2.0 in group 2 (P =0.03).

Analysis of the patients with exudative recurrence (ER) in each group

There was no significant difference between the two groups concerning the number of patients with ER (six in group 1 and eleven in group 2; P =0.618). Five patients demonstrated one SMH recurrence and underwent repeat surgery (two in group 1 and three in group 2, P =0.894).

Considering the patients who had an ER, we found that patients in group 1 had a better mean VA evolution between the 1-month and 1-year examinations than group 2 patients (respectively, logMAR −0.38±0.48 and logMAR 0.34±0.67; P =0.025). For these patients, the number of anti-VEGF IVT was significantly higher in group 1 than in group 2 (4.2±1.3 vs 1.9±1.9) (P =0.045).

Discussion

In this study, we aimed to evaluate the influence of monthly vs. bimestrial follow-up examinations on the long-term results of surgical treatment of SMH associated with exudative AMD in terms of VA. SMH complicating neovascular AMD are associated with a very bad spontaneous functional prognosis, relating to SMH thickness and location [26], preoperative VA [27] and delay before management. PPV associated with rtPA submacular injection, fluid-gas exchange and postoperative prone position have shown short-term efficacy [17, 20, 25, 28].

For the analysis of postoperative VA evolution, we considered 1 month as a baseline to minimize the impact of surgery; patients with less than 1 year follow-up were excluded and we set the limit of visits between the two groups at 11 to obtain two comparable groups.

Our results show that the mean VA at 1 month and 1 year post-surgery examinations were not significantly different from the preoperative values and were not inferior to other studies [17, 25]. Treumer et al. had a similar preoperative value (logMAR 1.7) but found a better mean VA (logMAR 0.8) at 3 months (P =0. 0001) [25]. Auriol et al. reported a final mean VA of logMAR 1.193 with significant postoperative improvement (P <0.05) [17].

Similar to several previously reported studies, we found a tendency of VA to deteriorate over the long-term. Haupert et al. found a statistically significant improvement between the preoperative and first postoperative VA (P =0.004) but not between the preoperative and the final acuity (obtained 1 to 15 months after surgery) (P =0.16): Haupert suspected that continuous progression of the AMD was the cause of this secondary deterioration [19]. Treumer et al. evaluated the same surgical procedure as ours associated with two ranibizumab postoperative injections in the following 2 months, and a predominantly VA-driven re-treatment regimen for greater than 1 year; they found a mean VA worsening in the long-term follow-up, but did not discuss the follow-up frequency [25]. Chang et al. observed that the mean VA was improved 1-year postoperatively but less than at the 3-month postoperative examination (P <0.001); they stated that they could have had better VA results with a more regimented schedule for anti-VEGF injection [22]. Moreover, several authors demonstrated that good visual outcomes observed with anti-VEGF therapy in patients treated for exudative AMD without SMH were obtained in real life only with regular and close follow-up [29, 30, 31] including OCT imaging [29, 30, 32, 33, 34].

The main outcome of this study is that patients who had a monthly visit in the postoperative year demonstrated a VA improvement (group 1; logMAR −0.29±0.44) whereas those with “at least” a bimestrial visit (5<n <11) had a poorer VA (group 2; logMAR +0.42±0.73) with a significant difference between the two groups (P =0. 016). It is interesting to highlight that group 1 patients demonstrated a tendency for a poorer VA initially 1 month postoperatively vs. the preoperative follow-up examination (logMAR −0.03±1.35 vs logMAR −0.21±0.76 in group 2; P =0.83).

Considering the patients who demonstrated ER in the two groups, we observed that this VA differential evolution was obtained thanks to a greater number of IVT. Yet, scheduling IVT implies a good follow-up, which limits AMD progression.

In our study, 19 of 21 patients were followed by referring ophthalmologists and two patients were followed in our center for all follow-up. We reviewed all clinical and imaging data obtained from our external partners. Visual acuity, fundus examination, angiography and OCT features were the criteria used to indicate anti-VEGF reinjections.

We are aware that the fact that the follow-up was not performed in our reference center might create a bias. However, this is also the interesting point of the present study, which is based on real life practice.

Concerning the limits of our study, unlike Treumer et al., we did not perform systematic cataract surgery on all phakic patients [20]. The relatively low rate of successful displacement may be explained by insufficient post-surgery positioning or by the thickness of the hemorrhage not allowing it to be entirely diluted by the rtPA. This data shows that outcomes after this type of surgery are still difficult to predict. The other limitations of our study are its retrospective nature and small sample size.

The presence of blood-thinning treatment (33.3% of our patients versus 45% in Treumer et al. study [25]) was not associated with more hemorrhagic complications. The important number of vitreous hemorrhages could be explained by the SMH liquefied blood released into the vitreous cavity through the retinal puncture following the rtPA subretinal injection.

Systemic hypertension was found in 57.1% of patients whereas it was found in 35% to 45% of the population of this age in France [35]. Blood-thinning treatment was not associated with the number of hemorrhage recurrences. These two factors may be associated with SMH but this was not evidenced in our study.

To conclude, our results show the importance of a close, regular and monthly postoperative follow-up of SMH associated with AMD. If surgery is necessary, which is still in debate, to treat patients with recent SMH, subsequent monthly visits are mandatory to preserve vision. Thus, all the future studies aiming to define suitable indications of SMH surgery should be designed with a monthly follow-up. At the least, follow-up regularity should be reported.

Disclosure of interest

The authors declare that they have no competing interest.


 Article présenté oralement au congrès de la SFO .

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