Management of recurrent postoperative fungal endophthalmitis.

AIM: To report the management of recurrent postoperative fungal endophthalmitis (POFE) after failed pars plana vitrectomy (PPV) and antifungal therapy. SETTINGS AND
DESIGN: Tertiary Care Referral Centre in North India. Retrospective, single institution, interventional case-series.
MATERIALS AND METHODS: Six patients with microbiologically proven recurrent post-operative fungal endophthalmitis refractory to conventional management were included. The final recurrence was managed with intraocular lens (IOL) explantation and re-PPV. Main outcome measures included preserved globe anatomy, visual acuity and retinal status. 'Anatomical success' defined as preserved anatomy of the globe, and absence of signs of inflammation. Functional success defined as an attached retina and a best corrected visual acuity of better than 20/400.
RESULTS: Of the six cases of POFE, five were culture positive [Aspergillus flavus (1), Aspergillus fumigatus (2), Candida albicans (1) and Candida glabrata (1)] and one was smear positive for yeast. All recurred (mean recurrences, 4) despite a mean of 2.17 PPVs and intravitreal amphotericin B. No recurrences were observed after IOL explantation with re - PPV (median follow-up, 37 months). Pre-study defined criteria for successful 'anatomical' and 'functional' outcomes were achieved in 83.3% and 50% respectively.
CONCLUSION: This report highlights the effective role of combined IOL explantation with PPV in managing recurrent POFE.

Postoperative fungal endophthalmitis (POFE) following intraocular surgery is uncommon in the West, but has been reported[12345678] more frequently from India.[12]

Experience in managing POFE remains limited.[12345678] Intraocular lens (IOL) explantation has been reported anecdotally with corneal recurrence needing additional surgery.[9] Compared to older reports[2456] with poor outcome, recently, newer antifungal agents such as voriconazole/liposomal amphotericin B/caspofungin has shown promise.[1] The experience with these drugs in developing countries is limited due to economic reasons.[10]

We report our experience in managing recurrent post cataract surgery fungal endophthalmitis despite initial pars plana vitreous surgery (PPV) and intravitreal antifungal agents with re-PPV and IOL explantation.

Materials and Methods

This study is a retrospective chart review of six consecutive cases (six eyes) of microbiologically proven postoperative fungal endophthalmitis presenting to a tertiary care center in North India who presented with multiple recurrences. Our center serves as a tertiary eye-care referral hospital for a greater part of North India. The computerized database and records were reviewed for details including, demographic details, interval between cataract surgery and diagnosis of endophthalmitis, visual acuity, anterior and posterior segment signs of inflammation, microbiological survey, treatment given, number of recurrences, management of each episode, details of multiple interventions and final outcome.

Patients presenting with visual acuity of better than hand motions (HM) were subjected to a ‘tap and inject’ regime, involving, intravitreal antibiotics (vancomycin and ceftazidime, 1mg and 2.25 mg in 0.1 ml each respectively) after 0.2 ml of vitreous tap was sent for microbiological assays. Patients with visual acuity of less than hand motions were subjected to an initial pars plana vitrectomy (PPV) and intravitreal antibiotics (as above). Intraocular fluid in both scenarios was sent for Gram's Stain, KOH 10% mount, blood agar, chocolate agar and Sabouraud's Dextrose Agar (SDA) for fungal culture. One portion of the sample was transported for bacterial culture in blood agar and chocolate agar. The second portion was directly inoculated on two plates of the SDA and incubated at 25 degree C and 37 degree C for a period of 6 weeks.

All cases, which tested positive for fungi on smear, were taken up for PPV along with intravitreal injection of amphotericin B 5 micg and dexamethasone 400 micg at the end of surgery. All these patients also received systemic antifungal drugs (oral itraconazole 100 mg or fluconazole 200 mg twice a day). Topical antifungal (natamycin 5%) was added in all cases. Patients, post PPV, were given oral corticosteroid (0.5mg/kg once a day) starting on the first postoperative day and tapered within 4-6 weeks. The systemic antifungal therapy was continued for a minimum of 8 weeks with monitoring for possible side effects.

Recurrence in this series was defined as cases that showed a fresh recrudescence of vitreous inflammation, increased anterior chamber reaction or reappearance of hypopyon following management with the standard regimen of treatment, namely core PPV with intravitreal amphotericin B and steroid. Repeat intravitreal amphotericin B (5 micg) injection was considered in all these cases of recurrence (except in case 4 where Candida glabrata was isolated on culture, intravitreal voriconazole was given). If the inflammation persisted despite the intravitreal antifungal and steroid the patients were subjected to repeat PPV (cases 1, 2, 4, and 6). All recurrences following the repeat PPV were managed with PPV and IOL explantation.

The capsule was removed using a vitrectomy probe with 360 degree scleral depression using a cotton tipped applicator. Any capsular remnants left were cleared manually using an intraocular forceps. Thoroughness of capsular removal was then assessed by intraoperative indirect ophthalmoscopy coupled with 360° scleral depression.

After a minimum follow up of 15 months since the last intervention, the outcome was defined in terms of ‘anatomical’ and ‘functional’ success. ‘Anatomical success’ was defined as a preserved anatomy of the globe with absence of signs of inflammation. ‘Functional success’ was defined as an attached retina and a best corrected visual acuity of better than 20/400.

Institutional ethical committee approval was obtained for the retrospective chart review for this study. The study conforms to the tenets of the declaration of Helsinki (1975). All statistical analysis was performed using SPSS software version 15.0 for Windows (SPSS, Inc., Chicago, IL).

Results

Demography, clinical features and microbiology

The study included six eyes of six patients with fungal endophthalmitis following cataract surgery. There were three males and three females. The mean age was 53.7 years (range 31-72 years). No patient was immunocompromised. Two patients (case 3 and 6) had controlled diabetes on oral hypoglycemic agents and another, (case 5) had hypoparathyroidism. The demographic details of the patients are summarized in Table 1.

Table 1

Demographic details of patients with recurrent fungal endophthalmitis

All six patients had undergone cataract surgery with a posterior chamber IOL implantation at other centers. The type of cataract surgery and the duration of presentation with initial endophthalmitis are indicated in Table 1. The mean time interval between cataract surgery and diagnosis of endophthalmitis was 8.5 + 4.72 weeks, (median 7 weeks), (range 3-12).

Clinical features of each patient at the time of initial presentation including visual acuity, anterior and posterior segment findings and microbiological results are summarized in Table 2. The initial visual acuity ranged from light perception (LP) to 20/160. All six eyes were remarkable for significant anterior chamber cells and intense flare (100%) and fluffy fibrin coating the IOL surface (100%). Five of six eyes were smear and culture positive and one eye was only smear positive [Table 2].

Table 2

Clinical features at presentation of patients with recurrent fungal endophthalmitis

In these six eyes, there was a mean of 4.16 episodes (+1.72) of recurrences (range 2 to 7). The mean interval between each recurrence was 2.80 + 0.69 weeks (range 2 to 4 weeks). All recurrences were associated with significant anterior segment reaction, with or without a hypopyon [Fig 1-4]. Intense fibrinous material accumulated over the IOL surface and over the capsule in all cases. Maximum concentration of fungal elements was seen in the inferior portion of the capsular bag intraoperatively. Two cases showed growth of fluffy balls behind the IOL (cases 1 and 6).

Figure 1

Case 1: Anterior segment appearance at the sixth recurrence with thick plaque behind the intraocular lens

Figure 4

Case 6: (a) A hypopyon and a plaque behind the intraocular lens during the second recurrence (b) During fifth recurrence prior to intraocular lens explantation with diffuse plaque behind intraocular lens and posterior capsule (c) Post re-pars plana vitrectomy with intraocular lens explantation after 36 months (BCVA 20/40)

Case 2: Vitreous ‘fluffy’ exudates at initial presentation

Case 4: Corneal involvement in the phaco section (Candida glabarata)

A mean of 2 (+1.09) pars plana vitrectomies (range 1-4) were performed in each eye before a final vitrectomy with IOL explantation was carried out. The details of the recurrences and its management are summarized in Table 3.

Table 3

Management of recurrences

Clinical outcome

One eye (case 1) developed a retinal detachment with a severe grade of proliferative vitreo-retinopathy and no perception of light (NPL). Case 4 developed corneal infiltrates two months after the initial PPV. The corneal infiltrates worsened despite maximum medical management including intracameral amphotericin B (twice), intracameral fluconazole (twice) and oral voriconazole. He underwent annular keratoplasty seven weeks after the initial corneal involvement. Postoperatively, he received intracameral (once) and intravitreal voriconazole (once) with no improvement, necessitating a repeat PPV with IOL explantation (five months after the initial PPV). After IOL removal the eye remained quiescent for 11 months with counting finger visual acuity.

Case 3 had a good anatomical outcome but the visual acuity remained at counting fingers. Cases 2, 5 and 6 achieved good anatomical and functional outcomes [Table 4]. Overall anatomical success was observed in 5 of 6 eyes (83.3%) and functional success in 3 of 6 eyes (50%).

Table 4

Outcome following final pars plana vitrectomy and intraocular lens explantation

No recurrence of inflammation was noted following re-PPV and IOL explantation after a mean follow-up period of 39.33 + 23.59 months (range 15-80 months), (median 36.5 months). Visual outcome at the last follow-up ranged from NLP to 20/40 [Table 4].

Discussion

Compared to western literature, fungal endophthalmitis is reportedly more common in tropical countries like India.[11112] Large series have reported between 18.6% and 21.6% of postoperative endophthalmitis to be of fungal etiology.[1113] Although vitrectomy with concomitant intravitreal antifungal agents is considered to be the treatment of choice,[1] there are no guidelines for managing recurrent episodes of fungal infection.

At our center we have observed that fungal endophthalmitis contributes significantly to the proportion of post-operative infection cases.[11214] It is possible that being a tertiary care center with a referral population of 62-70 million of a predominantly rural belt contributes to this high incidence. Narang et al.[1] observed that fungal endophthalmitis could mimic bacterial infection and even present as early as 48 hours.

In this study, we present a series of six eyes of six patients of fungal endophthalmitis following cataract surgery with a mean of 4.16 recurrences. The median interval after cataract surgery at presentation was 7 weeks. These eyes showed persistent infection despite a mean of two vitrectomies and multiple interventions including the systemic and intraocular use of antifungal agents, even newer agents like voriconazole. Following a final vitrectomy and IOL explantation with careful removal of the capsule, we were able to prevent further recurrences for a median follow-up period of 36.5 months.

The role of IOL explantation in treatment of endophthalmitis has been previously reported for bacterial and fungal etiologies with mixed success.[1516171819] Recently, persistence of infection was reported by Durand et al.,[3] despite removal of the IOL, multiple vitrectomies and intravitreal amphotericin B injections Fusarium endophthalmitis was subsequently managed with oral voriconazole alone, whereas Aspergillus fumigatus required additional intravenous caspofungin.[3] In one of our patients (case 4) despite oral and intracameral voriconazole, the infection persisted until the IOL removal. The role of newer antifungal agents in the management of recurrent cases needs further long-term, prospective trials.

We speculate that the fungal spores are sequestered over the IOL surface and in the capsular bag and are responsible for the multiple recurrences. There is evidence to suggest that fungal filaments survive on the surface of IOL[20] and in the capsular bag.[6] In all our cases intraoperatively we noted a maximum concentration of fungal elements in the inferior portion of the capsular bag which was completely removed. Perhaps the complete capsulectomy in our series contributed to the successful outcome.

Corneal involvement in fungal endophthalmitis has been reported to be a poor prognosis indicator.[19] In our case series one patient (case 4) had significant corneal involvement, requiring annular corneal graft. Recurrence after keratoplasty necessitated a re-PPV with IOL explantation. No further recurrences were noted (follow-up 11 months).

Late onset fungal endophthalmitis has been associated with poor outcome[4569] sometimes even resulting in ocular atrophy.[56] In this series an overall anatomically good outcome was achieved in 83.3% (5/6 eyes) and ‘functional’ success was achieved in 50% (3/6 eyes). In a large series good functional outcome was reported in 37.04%.[1] Corneal involvement was considerably higher in that study compared to ours (51.8% vs. 16.7%).

The limitations of this study need to be highlighted. Persistence of the disease especially from sequestered fungal elements within the capsular bag or on the surface of the IOL, could also account for some of these recurrences. Although each new episode of infection followed a clinical quiescence of inflammation, there is no way to accurately distinguish a true recurrence from low-grade persistence. This small series is derived from varying pre-operative and environmental conditions precluding any comparison of risk factors. Each case was managed individually, with no homogenous protocol for intervention leading to the IOL explantation precluding the comparison of the relative merits of each procedure. However, in view of the rarity of such multiple recurrences refractory to the accepted standard of management, it is of value that the final procedure resulted in elimination of infection.

Conclusion

Re-pars plana vitreous surgery with IOL explantation with complete capsulectomy seems to be effective in a setting of persistent and recurrent microbiologically proven fungal endophthalmitis. Prospective long-term studies in larger series are necessary to establish this modality as a standard of care.