Dr. Abhishek Dave, D15582
ABSTRACT
PURPOSE: To study the microbiological profile, prognostic factors and outcomes of surgery for microbial keratitis (MK) associated endophthalmitis.
METHODS: Retrospective analysis of 39 MK associated endophthalmitis cases which underwent combined PKP with VR surgery.
RESULTS: Majority (84.6%) patients had a history of previous ocular surgery, cataract surgery being most common (51.2%). Six patients had history of trauma & 8 patients had corneal graft infection. Culture positivity rate was 92.3%. Organisms isolated were Streptococcal sp (20.5%), Pseudomonas (15.3%) Staphylococcal sp (12.8%) & Fungus (35.8%). Final visual acuity ranged from NPL to 20/120. Poor anatomic success was seen in 15(38.46%) eyes (9-phthisis, 6-eviscerated). Fungal cases had poor success rate (P-0.02).
CONCLUSION: MK associated endophthalmitis is a sight threatening ocular condition. Fungal etiology carries a poorer prognosis. Timely surgical intervention can achieve favourable anatomical and functional results
KEY WORDS: Microbial keratitis, endophthalmitis, penetrating keratoplasty, pars plana vitrectomy
INTRODUCTION
Infective endophthalmitis is a sight threatening ophthalmic emergency. The management becomes more challenging and the prognosis poorer if endophthalmitis is associated with microbial keratitis (MK) or any corneal pathology obscuring posterior segment visualization.1 Though endophthalmitis as a complication of MK is uncommon in healthy eyes, it has been reported that 0.7-1.7% of MK can progress to endophthalmitis.2 Majority of these eyes need evisceration/ enucleation for eliminating the infection and many of them as a primary treatment.1,3 Management with combined penetrating keratoplasty (PKP) and pars plana vitrectomy (PPV) is helpful in such eyes associated with corneal opacity/infection, which causes insufficient visualization of the fundus. Previous studies have reported favourable outcomes of combined PKP and vitreoretinal surgery using a temporary keratoprosthesis.4-9 But most of these studies have included non infectious causes of combined anterior and posterior segment diseases. Dae Sung Lee et al in their retrospective case series of 11 eyes reported the outcomes of patients who underwent combined PKP and vitrectomy. Six of their 11 patients had infectious endophthalmitis with either microbial keratitis or corneal edema obscuring posterior segment visualization. All 6 eyes had poor final visual outcome with only one eye maintaining clear graft and one eye progressing to phthisis bulbi. But in 4 of the 6 cases the globe could be salvaged.6 In this study we describe a series of patients with microbial keratitis associated endophthalmitis. These patients underwent combined PPV and PKP with or without temporary keratoprosthesis (TKP). We analyzed their microbiological profile and anatomic and functional surgical outcomes.
MATERIAL AND METHODS
A retrospective analysis of medical records of patients with microbial keratitis associated endophthalmitis who underwent combined penetrating keratoplasty with pars plana vitrectomy at a tertiary care eye hospital was done. Institutional Review Board approved the study protocol. Records of 55 eyes of 55 patients, operated between January 2010 and August 2016 were analyzed. Inclusion criteria were patients with age more than 14 years with diagnosed endophthalmitis, with microbial keratitis with poor corneal clarity so as to impede intraoperative posterior segment visualization. Patients with minimum follow-up of 6 months were included in the study. Diagnosis of endophthalmitis was clinical, supplemented with ultrasonic B-scan findings confirming vitreous exudation. Patients with age less than or equal to 14 years and a follow up of less than 6 months were excluded from the study. Patients with associated retinal detachment were also excluded. Patients with no perception of light underwent primary evisceration and were also excluded. Thirty nine of 53 patients fulfilled the inclusion criteria and their data was documented. The baseline characteristics of the patients, including age, gender, time lag between symptoms and presentation, inciting factor, ocular diagnosis (corneal and retinal), previous ocular procedures, Visual Acuity (VA), Intraocular Pressure (IOP), lens status and status of the vitreous and retina (based on B-scan ultrasound) were documented. Intraoperative details like use of temporary keratoprosthesis (TKP), graft size, lens or IOL extraction, intravitreal antibiotic injection, silicone oil insertion or any other extra procedure were noted. The microbiological profile of vitreous sample and corneal button were documented. Post operative data analyzed were VA (UCVA and BCVA), IOP, lens status, graft clarity and status of the retina postoperatively on day 1, month 1 and 6, and yearly until the last follow-up visit. Any additional surgery performed or intravitreal injection was also documented. Any complication or recurrence of infection was noted.
Anatomic and functional outcomes were defined prior to review. Since all patients presented with beyond Snellen acuities [i.e., count fingers (CF), hand movements (HM), perception of light (PL) or no perception of light (NPL)], visual results were obtained from the difference in VA pre-treatment and post-treatment and categorised into three groups: (1) improved, (2) no change, and (3) deteriorated. An improvement was defined as either a gain of one measured step or more (e.g., from HM to CF, or CF to 20/100). A deterioration was defined as loss of one measured step or more (e.g., from CF to PL). Anatomic success was defined as elimination of infection with restoration of tectonic integrity. Retinal anatomic success was defined as resolution of vitreous exudation with attached retina. Corneal success was defined on the basis of a clear and compact graft, and any instances of graft rejection or failure were noted. Anatomic failure was considered when the eye progressed to phthisis bulbi or needed evisceration for uncontrolled infection. All data were collected in an Excel data sheet (Microsoft, Redmond, WA).
Surgical Technique
Written informed consent was taken. After adequate anaesthesia was obtained with a Van Lint facial block and a peribulbar injection, a lid speculum was inserted. Three eyes were operated under general anesthesia. A 360 degree peritomy was performed. A Flieringa ring was secured to the sclera with four 6-0 black silk interrupted sutures. A 20- gauze infusion port was inserted at the pars plana and sutured to the sclera. Two more ports were prepared at the pars plana with an MVR blade and temporarily closed with metal plugs. The affected portion of the cornea was excised with a corneal trephine (Madhu Instruments, India) of diameter 7.25 or 8.25mm depending on the size of the pathology. A Landers third generation TKP (Ocular Instruments, Bellevue, WA, USA) of 7.2 or 8.2mm in diameter, was sutured onto the recipient cornea with six interrupted 9-0 nylon sutures. In case the corneal infiltrates were larger than 8.2 mm the vitrectomy was performed after placing a corneal allograft and securing it with 16-24 interrupted 10-0 or 9-0 nylon sutures. Standard three-port pars plana vitrectomy was then performed. Cataract was removed by pars plana lensectomy or extracapsular cataract extraction; intraocular lens was removed it was infected or was decentred and distorted the view of the posterior segment. Depending on the retinal pathology, vitreoretinal surgery was performed. In case a TKP was placed, it was later removed and replaced with donor corneal button with diameter 0.5mm larger than the host trephination. The donor cornea was sutured onto the recipient cornea with 16-24 interrupted 10-0 nylon sutures. During PKP, intraocular pressure was adjusted by regulating the flow through the infusion port. All corneal suture knots were buried. Intraocular pressure was slowly brought to normal. Silicon oil would be injected at this stage if indicated. After closure of the sclerostomy site and peritomy, 20 000U of gentamicin was injected subconjunctivally. Vitreous aspirate and corneal button were plated on blood agar, chocolate and Sabouraud dextrose agar for bacterial and fungal cultures.
Postoperatively, patients were prescribed oral antibiotics (ciprofloxacin, 500 mg twice daily), topical antibiotics (cefazolin sodium 5% and tobramycin sulfate 1.3%, 2 hourly), and topical steroids (prednisolone acetate 1%, 4 hourly) in cases of bacterial endophthalmitis. Topical natamycin (5%, 1 hourly) and oral ketoconazole (200 mg, 12 hourly) were given for fungal keratitis (topical steroids were withheld in fungal keratitis). Antibiotics were changed based on culture-sensitivity results. Patients were followed up regularly on case to case basis till the infection resolved, then monthly for 3 months, 2 monthly for 1 year, and 4 monthly thereafter. Any additional procedure or intravitreal injection needed to control the infection was performed.
Statistical Analysis
SPSS software version 18.0 (SPSS, Inc, Chicago, IL) was used for statistical analysis. For description, quantitative variables have been expressed as mean ± SD, and qualitative variables have been expressed as a percentage. The x2 tests were performed for categorical variables. All the tests were 2-tailed, and P<0.05 was considered significant.
RESULTS
Combined PKP with PPV for infectious endophthalmitis was performed in 53 eyes of 53 patients during the defined study period. Of these, 39 eyes met the inclusion and exclusion criteria [24 male, 15 female; age 53.39±12.94 (21–77) years] and were evaluated. The mean follow-up period was 16.37±7.31 (6-36) months. The average time of presentation was 13.53±13.28 (2-60) days after the initial appearance of symptoms.
Pre-Operative Characteristics
The inciting agent for endophthalmitis was recent surgical intervention in 25 eyes (64.1%), corneal graft infection in 8 eyes (20.51%), trauma in 6 eyes (15.38%). A history of past ocular surgery was present in 33 of 39 eyes (84.6%). Of these the most common surgery was cataract extraction with or without intraocular lens (IOL) placement in 20 eyes (51.2%). Other surgeries which had been performed in the past were IOL dialling or explantation in 2 eyes (5.1%), vitreo-retinal surgery in 1 eye (2.56%), corneal laceration repair in 2 eyes (5.1%) and PKP in 8 eyes [ 18.60% (6-optical PKP and 2 therapeutic PKP). One eye (2.32%) had undergone tissue adhesive with bandage contact lens placement for a small corneal perforation. Nineteen patients had associated systemic illness (diabetes mellitus: 9, ischaemic heart disease: 4, and hypertension: 12).
All eyes had microbial keratitis precluding adequate visualization of the vitreous and retina. B-scan performed on presentation was suggestive of endophthalmitis. Lens examination revealed presence of crystalline lens in 4 eyes (10.25%), pseudophakia in 27 eyes (69.23%) and aphakia in 8 eyes (20.51%).
The preoperative VA was PL in 35 eyes (81.39%), HM in 5 (11.62%) eyes and CF (6.97%) in 3 eyes with a median VA of PL. Eleven out of 43 (25.58%) patients were monocular and had a vision less than 20/400 in the fellow eye also.
Intra Operative Characteristics
Pars plana vitrectomy was carried out using a TKP in 17 eyes (43.58%) and through a clear allograft in 22 eyes (56.41%). Corneal graft size varied from 7.5-11 mm (Median – 8.5mm). An extracapsular cataract extraction was done in 4 eyes and IOL explantation in 22 eyes. Intraocular foreign body removal was done in one eye. Silicone oil insertion (SOI) was done as a primary procedure in one eye, and 3 other eyes needed SOI in subsequent surgeries. Microbiological culture positivity was seen in 36 eyes (92.3%). Bacterial growth was observed in 22 eyes (56.41%) and fungus was isolated in 14 eyes (35.89%). There was no growth documented in 3 eyes (7.69%). Bacterial organisms isolated were Staphylococcus aureus(5 eyes), staphylococcus epidermidis(2 eyes), streptococcus sp(4 eyes), Streptococcus pneumonia (3 eyes) Pseudomonas aeruginosa(6 eyes), Moraxella sp(1 eye), Klebseilla sp(3 eyes), Corynebacterium diptheriae(2 eyes). Mixed bacterial growth was observed in 3 eyes. Fungus isolated were Aspergillus(7), Fusarium (4), Dematicious fungus(2), Cladosporium (1 eye).
Post Operative Results
At the last follow-up visit the BCVA improved in 16 eyes (41.02%), did not change in 14 eyes (35.89%) and deteriorated in 9 eyes (23.07%). Final BCVA were PL in 10, HM in 1, CF in 2, between 20/1200 to 20/400 in 9 eyes, between 20/400 to 20/200 in 8 eyes and above 20/200 in 2 eyes. No light perception was noted in 7 eyes.
Anatomical failure was seen in 15 eyes (38.46%) of which 9 developed phthisis bulbi and 6 eyes had to be eviscerated. Out of the 15 eyes having anatomical failure, 8 eyes (53.33%) had fungal infection. Globe survival was significantly worse when fungus was isolated as the causative agent for infection as compared to bacterial infection (P=0.02). Visual acuity outcomes were also significantly poorer when fungus was implicated as the infective organism (P=0.02). Of the 24 eyes which maintained anatomical integrity, corneal graft was clear in 17 eyes (70.83%). Persistent epitheial defect over the cornel graft was noted in 3 eyes, which healed with permanent lateral tarsorraphy.
Retinal anatomic success was achieved in 28 eyes (71.79%) at final follow-up. The infection failed to clear in 11 (28.20%) eyes in spite of repeated surgical attempts. Six of these eyes were eviscerated and the rest progressed to phthisis bulbi as the patients did not consent for evisceration. Three eyes developed retinal detachment and all 3 developed phthisis bulbi eventually. Epi-retinal membrane formation was seen in 3 eyes. At the final follow-up 33 (84.61%) patients were aphakic and 6 (15.38%) patients were pseudophakic. The mean intraocular pressure (IOP) in the eyes which maintained anatomical integrity was 12.71± 4.39 mmHg. Raised IOP was seen in 2 eyes which was controlled on topical anti-glaucoma medications.
Repeat surgical intervention was seen in many eyes. The most common intervention was injection of intra-ocular antibiotics, which was done in 19 eyes (48.71%). A repeat PPV was needed in 5 eyes (12.82%) and repeat PKP with PPV was needed in 2 eyes (5.12%). Of the 11 patients who had poor vision in the fellow eye, 8 eyes could be salvaged and 7 of those had BCVA above CF at 1metre.
DISCUSSION
The main goal of treatment for infective endophthalmitis with microbial keratitis is the eradication or reduction of infective load and preservation of structural integrity of the eye. Visual rehabilitation is often difficult and of secondary consideration. Visual outcomes of endophthalmitis are often poor, with one third of individuals not gaining vision better than counting fingers, and 50% not able to recover vision better than 20/40.10 The prognosis becomes much poorer if it is associated with microbial keratitis or corneal opacification. In our study we evaluated the results of 39 eyes which underwent combined PKP with PPV with a minimum follow-up of 6 months. 24 eyes (61.53%) could be salvaged and 16 (41.02%) eyes noted an improvement in visual acuity. This was of particular importance in 7 of the 11 monoocular patients who became self ambulatory following the surgery.
Several retrospective studies have reported the outcomes of combined PKP and vitreoretinal surgery. The largest of these studies was by Dong et al, which included 107 eyes with coexisting corneal and vitreoretinal disease.4 They reported an eye salvage rate of 86%. But only 5 of these eyes had endophthalmitis with corneal infection. Tanaka et al reported the results of combined surgery in 15 eyes with a generally poor visual outcome.5 Their series had 7 cases of fungal endophthalmitis with no corneal infection. Three of these eyes progressed to phthisis bulbi, but the rest achieved a favourable visual outcome. In their series of 11 eyes, Dae Sung Lee et al included 6 cases of endophthalmitis of which 4 had MK also.6 Of these 2 eyes progressed to phthisis bulbi, two eyes had NPL vision and only one eye had an improved vision post operatively. Various other studies evaluating combined surgeries for non-infective pathologies have been done. Roters et al reported the outcomes of combined surgery in 34 severely injured eyes. 74% of these eyes attained final VA better than the preoperative VA.8 None of these eyes had an infectious pathology. Similarly Roters et al again reported the outcomes of 53 eyes which underwent combined surgery with silicone oil insertion.7 Only one of these eyes had a perforated corneal ulcer and none had endophthalmitis. Visual acuity remained same or improved in 73% of the eyes. Thus most of the previous studies have evaluated the outcomes of combined surgeries in majorly non-infective pathologies. Our study is unique in addressing the results of surgical intervention in endophthalmitis with majority of cases (88%) having an associated microbial keratitis. Our results may be modest as compared to previous studies as management of combined anterior and posterior segment infection is a challenging task. However, if we compare our results with those of Tanaka etal and Dae Sung Lee et al our outcomes are relatively better. The reason for it could be that we managed our cases very aggressively with early surgical intervention, close in-patient postoperative follow-up, intensive topical and systemic treatment and frequent injection of intravitreal and intracameral antibiotics. A resurgery was performed as soon as there was any evidence of residual or recurrent infection.
MK-associated endophthalmitis only accounts for up to 6–10 % of exogenous endophthalmitis.11 The rate of development of endophthalmitis in patients with MK has been reported to be in the range of 0.7% to 1.7% and often carries a poor visual prognosis.2 Majority of the eyes in our study had undergone a previous ocular surgery, including complicated cataract surgery and PKP. Any discontinuity in the posterior capsule provides a tract for the microbes to travel to the posterior segment even with a trivial anterior segment infection18. Corneal sutures could also be a predisposing cause of keratitis progressing to endophthalmitis19 Previously O’Neill et al have reported the risk factors, microbial profiles and prognosis of MK associated endophthalmitis in high-risk eyes.1 They noted poor visual outcomes and majority (62.2%) of the eyes needed evisceration/enucleation. None of their cases were taken up for vitrectomy and were managed medically. We found our globe salvage rate to be relatively better. One reason for it could be early surgical intervention in all the cases which helps in de-bulking the infectious load.
The microbiological culture positivity seen in our study (92.3%) was slightly higher than that reported in previous series of combined MK and endophthalmitis.1,2. In our study nearly one-third of eyes showed fungus on microbiological evaluation. Only Tanaka et al have reported on combined surgery in fungal endophthalmitis.5 Most other studies on MK related endophthalmitis have reported bacterial growth only. Fungus is an important cause of ocular infection in India accounting for nearly 35% of keratitis cases11 and 7.1-12.7% of endophthalmitis cases in Asian countries12. We found a statistically significant poorer outcome in fungal infection which is supported by previous studies on fungal keratitis.13 Similar to previous studies the most common implicated bacteria were Streptococcus species (20.93%) followed by Staphylococcus species (16.27%) and Pseudomonas (13.95%) and other bacterial organisms.1,11,14,15,16
Landers et al reported the first use TKP for posterior segment disease with associated corneal opacification in 1981.19 Since then several studies have reported outcomes of combined PKP with vitreoretinal surgeries using TKP.4-9 We preferred using the Landers TKP in comparison to Eckardt’s as it provides a good view of the central retina and vitreous which is needed for core vitrectomy.20 A TKP maintains a closed globe system with normal IOP to allow easy performance of vitreo-retinal procedures without major complications. We could use the TKP in only 17 of 39eyes (43.58%) as the size of corneal infiltration was much larger in the rest of the eyes, precluding the usage of a TKP. Though we could achieve a similar closed globe system after suturing a corneal allograft, but the results were poorer without the use of a TKP. The possible reason for it could be the larger graft size needed for these eyes and also more extensive corneal infiltration making the prognosis worse as such.21
Our retrospective study does have some limitations. First is the relatively small sample size. But seeing the unusual occurrence of such complex pathologies and relative absence of literature on combined surgeries for infectious endophthalmitis and MK our series is the largest to the best of our knowledge. Second is the varied strategy for post-operative management. Since there are no specific protocols for management of such complicated cases exists, we adopted a case based management approach.
To summarize, combined penetrating keratoplasty and pars plana vitrectomy is an effective way of managing endophthalmitis with microbial keratitis. Visual prognosis is guarded because of extensive tissue destruction and the primary aim of the surgery is restoration of the structural integrity of the eye. Fungal infection carries a poorer prognosis. Aggressive approach with early surgical intervention, close in-patient postoperative follow-up, intensive topical and systemic treatment and frequent injection of intravitreal and intracameral antibiotics helps in achieving a favourable outcome.
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- Scott IU, Flynn HWJr, FeuerW, Pflugfelder SC, Alfonso EC, Forster RK, Miller D (1996) Endophthalmitis associated with microbial keratitis. Ophthalmology 103:1864–1870
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- Roters S, Hamzei P, Szurman P, et al. Combined penetrating keratoplasty and vitreoretinal surgery with silicone oil: a 1-year follow-up. Graefes Arch Clin Exp Ophthalmol. 2003;23(1):48–56
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- Lalitha P, Rajagopalan J, Prakash K, Ramasamy K, Prajna NV, Srinivasan M. Post cataract endophthalmitis in South India incidence and outcome. Ophthalmology 2005 Nov;112(11):1884-9
- Rogers GM, Goins KM, Sutphin JE, et al. Outcomes of treatment of fungal keratitis at the University of Iowa Hospitals and Clinics: a 10-year retrospective analysis. Cornea. 2013;32:1131–1136
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- Panda A, Satpathy G, Nayak N, Kumar S, Kumar A (2007) Demographic pattern, predisposing factors and management of ulcerative keratitis: evaluation of one thousand unilateral cases at a tertiary care centre. Clin Experiment Ophthalmol 35:44–50
- Moore NM, Flaws ML (2011) Epidemiology and pathogenesis of Pseudomonas aeruginosa infections. Clin Lab Sci 24:43–46
- Wong TY, Chee SP. The epidemiology of acute endophthalmitis after cataract surgery in an Asian population. Ophthalmology 2004;111:699-705
- Khurshid GS, Fahy GT. Endophthalmitis secondary to corneal sutures: series of delayed-onset keratitis requiring intravitreal antibiotics. J Cataract Refract Surg. 2003 Jul;29(7):1370-2
- Landers MB, Foulks GN, Landers DM et al. (1981) Temporary keratoprosthesis for the use during pars plana vitrectomy. Am J Ophthalmol 91:615–619
- Eckardt C (1987) A new temporary keratoprothesis for pars plana vitrectomy. Retina 7:34–37
- T Sharma N, Jain M, Sehra SV, Maharana P, Agarwal T, Satpathy G et al. Outcomes of therapeutic penetrating keratoplasty from a tertiary eye care centre in northern India. Cornea. 2014 Feb;33(2):114-8


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