Introduction

Endophthalmitis is defined as an inflammation of the inner layers of the eye with exudation in the vitreous cavity resulting from intraocular colonization by microorganisms. It can be exogenous or endogenous. It is an ocular emergency with poor visual prognosis and multifactorial etiology. Endogenous endophthalmitis is much less common than exogenous endophthalmitis and is estimated to account for 2% to 8% of all endophthalmitis cases.^1,2 It occurs when bacteria or fungi are hematogenously disseminated into the ocular circulation. The visual prognosis is often poor. The risk of septicaemia with a mortality rate of 5-15%.² is reported, and therefore a prompt diagnosis of the underlying cause of endogenous endophthalmitis along with the control of eye infection is of utmost importance.

Risk factors

Endogenous endophthalmitis has multiple factors playing a role in its occurrence. (Table 1) The following are the risk factors for endogenous endophthalmitis- long-term indwelling catheters, intravenous drug abuse (IVDA), chronic immunosuppression (cancer, acquired immunodeficiency syndrome, and organ transplants), debilitating diseases (diabetes mellitus, renal failure, and liver cirrhosis), endocarditis, or urinary tract infections. ^3-6 The most common risk factors reported from Southeast Asia being uncontrolled diabetes and hepatobiliary diseases in contrast to indwelling urinary, intravenous catheters or systemic immunosuppression reported from the Western countries.^7-10 Endogenous endophthalmitis has an extraocular source of infection like- tooth abscess, pneumonia, endocarditis, urinary tract infection, meningitis, and liver abscess.⁴

In the COVID-19 era the incidence of both bacterial and fungal endogenous endophthalmitis drastically increased due to long duration of admission in intensive care units, the immunocompromised state of the patients, diabetes secondary to high dose systemic steroids given to treat pneumonia and intravenous lines maintained for several days to treat these sick patients.¹¹ In a multicentre retrospective database review Agarwal et al described 6 patients who developed endogenous endophthalmitis as a complication of COVID-19 infection. Four out of their six patients were culture positive, two for bacterial pathogen and two for fungal pathogen.¹¹ In another case series by Shah el al four cases of presumed fungal endogenous endophthalmitis were described in patients who recovered from COVID-19.⁶⁴ Shroff et al described in their case series of 5 patients with severe COVID-19 infection with prolonged hospitalization and treatment with corticosteroids who developed endogenous endophthalmitis, and a fungal pathogen was identified as the causative agent for endophthalmitis in five out of the seven eyes reported.⁶⁵ In the COVID era, patients who presented with intraocular inflammation were often misdiagnosed as patients of uveitis and later on upon no response to treatment, were diagnosed to have endogenous endophthalmitis secondary to bacterial or fungal infection leading to a delay in their appropriate treatment.

Etiology

The infecting microorganism travels via the bloodstream and multiplies in the choroid, thereafter infiltrating the retina and spreading into the vitreous.¹² There are several risk factors and causative microorganisms causing Endogenous endophthalmitis. (Table 2)

A vast variety of bacteria are responsible for causing endogenous endophthalmitis. The most common being gram-positive organisms such as Streptococcus species (endocarditis), Staphylococcus aureus (cutaneous infections), Bacillus species (from intravenous drug use), and Nocardia species (in immunocompromised patients). The most common gram-negative organisms are Neisseria meningitidis, Haemophilus influenzae, and enteric organisms such as Escherichia coli and Klebsiella species. A study by Jackson et al reported that in Asia, patients with liver abscess, have an infection from Klebsiella species as the most common cause of endogenous endophthalmitis.⁴ Some Asian studies have reported approximately 11.1 to 17.54 % of total cases of endogenous endophthalmitis to be having fungal aetiology, and the rest having bacterial aetiology.^13-14

The most common yeast isolate and the most common overall fungal isolate in patients with endogenous fungal endophthalmitis is Candida albicans.^15-16 Intravenous drug abuse has a strong association with endophthalmitis caused by Candida.¹⁷ It has been reported that in patients with candidemia, rates of endogenous endophthalmitis range from less than 3% to 44%.¹⁸ The most common mould isolate and the second most common overall fungal isolate in patients with endogenous fungal endophthalmitis is Aspergillus.¹⁵ Other less common causes of fungal endogenous endophthalmitis are Histoplasma capsulatum, Cryptococcus neoformans, Sporothrix schenckii, and Blastomyces dermatitidis.¹⁹

Clinical features

Patients having endogenous endophthalmitis usually present with varying degrees of pain, redness, photophobia, floaters and vision loss. Classic signs include eyelid oedema, conjunctival injection, and circumcorneal congestion. A detailed slit lamp examination should be done, which may show corneal oedema, anterior chamber reaction with hypopyon, pupillary distortion secondary to synechiae formation, absent red reflex, and vitreous cells.^20-24 (Figure 1) Fundus examination may show vitreous haze and exudates, retinal haemorrhages, and vasculitis. Small microabscesses in the retina or choroid may be found rarely. Sometimes, both eyes may be affected simultaneously as the ocular infection is secondary to a systemic spread. (Table 4)

Bacterial Etiology should be suspected in patients with rapidly progressive and intense intraocular inflammation. All the clinical signs are more evident in bacterial endogenous endophthalmitis in comparison to fungal endophthalmitis which has a more insidious onset, focal vitreous opacities, and chorioretinal infiltrates. (Table 5)

The most characteristic clinical sign of Candida endophthalmitis is the presence of one or more creamy white, well-circumscribed chorioretinal lesions, less than 1 mm in diameter, most commonly in the posterior pole, with an overlying haze of vitreous. Yellow or fluffy-white vitreous opacities connected by strands of inflammatory material known as “string of pearls.”²⁵ (Figure 2) If the media haze permits, then an optical coherence tomography(OCT) of the lesion can depict the vertical spread of the Candida into the vitreous from the retina.²⁶

Aspergillus endophthalmitis shows a characteristic central macular chorioretinal inflammatory lesion.²⁷ A Pseudohypoyon i.e a gravitational layering of inflammatory exudates in either the preretinal (subhyaloid) or subretinal space may be noted with the macular lesion.(Figure 3) The other associated features are retinal vascular occlusion, choroidal vascular occlusion, exudative retinal detachment, and/or diffuse hemorrhagic retinal necrosis.^28-29

Figure 3 Ultrasound B scan showing Sub retinal abscess over posterior pole in a patient with Aspergilllus endogenous endophthalmitis.

Endogenous endophthalmitis presents with a variety of clinical features and can mimic various other ocular conditions enumerated in table 3.

Management

Management of a patient of endogenous endophthalmitis involves evaluation of degree of ocular involvement, identification of the causative organism, and the underlying primary source of infection followed by the treatment of both the endophthalmitis and the underlying systemic infection.

A note is made of the best corrected visual acuity at presentation. A thorough ocular examination with proper documentation of each finding is vital to monitor the response of the patient.

A referral to an internist for a systemic evaluation to locate the underlying primary source of infection is of paramount importance.

Proper counselling of the patient regarding the visual prognosis and the goals of treatment with an informed consent in place before any intervention helps to avoid medico legal issues.

Ocular Investigations

Ultrasound B Scan

Indication: Posterior segment is not visible due to media haze. (Figure 3-5)

Findings: low to moderately reflective dot and membranous echoes in the vitreous cavity, rarely exudative retinal detachment is seen with a high reflective membrane attached to the optic nerve head with limited after movements and evidence of shifting fluid. There can be evidence of choroidal abscesses which can be seen as dome-shaped lesions arising from the choroid (Fig. 1)

OCT- Optical Coherence Tomography

Indication: If the media haze permits and lesion is seen on the posterior pole

Findings: Posterior vitreous cells, cystoid macular edema, retinal or sub retinal abscess,^30-31 choroidal thickening.^31-32

Investigations performed to collect a sample for microbiological examination to know the causative micro-organism and its drug sensitivity

1. Blood culture- sample to be collected prior to starting systemic antibiotics
2. Urine routine and culture with sensitivity
3. Anterior chamber tap- perform prior to starting any topical antibiotics. Take an informed consent and perform under strict aseptic precautions under topical anaesthesia. Place a sterile lid speculum to avoid any contamination from the eyelashes. Use a 26-gauge needle mounted on a 2 ml syringe and collect a sample of the aqueous preferably hypopyon.
4. Diagnostic vitrectomy- informed consent, strict aseptic precautions and local anaesthesia are used. Micro incision vitrectomy (MIVS) is used to perform a diagnostic vitrectomy. Preferably an undiluted sample of the vitreous is collected by using air infusion in place of saline during vitrectomy. Sample of the vitreous should be collected near the lesion which has maximum yield. The sample is plated on culture plates preferably in the operation theatre.
5. Real-time polymerase chain reaction (RT-PCR) of aqueous and vitreous samples may also be considered specially when suspecting a viral etiology.

Systemic Pharmacotherapy

Bacterial Endogenous Endophthalmitis

Patients with bacterial endogenous endophthalmitis are started on broad spectrum systemic antimicrobials for the management of systemic infection. Commonly used drugs are oral ciprofloxacin (750 mg twice a day)⁷ or intravenous cefotaxime (1 g thrice a day), and intravenous gentamycin (80 mg twice a day)⁶. Infectious disease specialist or a physician should be consulted for the choice of appropriate systemic antibiotics which are then modified according to the culture and sensitivity report.

Fungal Endogenous Endophthalmitis

Amphotericin B is administered intravenously and is effective in the treatment of infections due to Candida,³³ Aspergillus,³⁴ Blastomyces,³⁵ Coccidioides,³⁶ and other fungi. It is associated with dose limiting nephrotoxicity, hypotension, arrhythmias, and infusion-related fever and chills when used systemically.³⁷

Among the azoles, the recommended dose of fluconazole according to the Infectious Disease Society of America (IDSA) guidelines for Candida endophthalmitis is 400–800 mg daily³⁸. It has better side effect profile than AMB and is a broad spectrum anti-fungal. Hence it is used as the first-line agent against fungal endogenous endophthalmitis as shown by Hamada et al.³⁹

For the treatment of Candida endophthalmitis administration of amphotericin B along with flucytosine is recommended by IDSA.³⁹

Fluconazole (with or without PPV) has also been reported to successfully treat endophthalmitis caused by C. tropicalis,⁴⁰ Coccidioides immitis,⁴¹ and Cryptococcus neoformans.⁴² Apart from the gastrointestinal disturbance as the major reported toxicity, it is otherwise well tolerated.⁴³ Patient having Chorioretinitis outside the posterior pole oral fluconazole may be an appropriate choice of antifungal⁴⁴

Voriconazole is a synthetic second-generation azole derived from fluconazole. It is generally effective against most Candida species (including those resistant to fluconazole, such as C. krusei and C. glabrata),⁴⁵ as well as Aspergillus and Cryptococcus.⁴⁶ It has an excellent intravitreal penetration from the systemic circulation.⁴⁷ It can be administered orally as well as intravenously.

Patients having Endogenous endophthalmitis caused by Aspergillus require aggressive treatment in the form of diagnostic and therapeutic pars plana vitrectomy in conjunction with intravitreal injection of amphotericin B or voriconazole and oral voriconazole or intravenous amphotericin B.⁴⁷

The minimum duration for which the systemic antifungal therapy should be administered is six weeks but the period of therapy depends upon the response and resolution of ocular lesions. A longer duration of therapy may be required for patients with severe ocular involvement.

Intravitreal Pharmacotherapy

Bacterial Endogenous Endophthalmitis

Initially patient is administered empirical intravitreal antibiotics covering both gram-positive and gram-negative micro-organisms, when the etiology is unknown. This empirical treatment consists of vancomycin 1 mg/0.1 ml along with ceftazidime 2.25 mg/0.1 ml .^21,48,49 Vancomycin is the drug of choice for gram-positive infections, as it also covers methicillin-resistant organisms.²¹ Ceftazidime (2.25 mg/0.1 ml) is the preferred drugs for covering gram negative microorganisms. ^21,50 The half-life of intravitreal antibiotics is short, and repeated injections may be required. After the microbiology culture and sensitivity report of the vitreous and blood samples comes the drugs are accordingly modified.

Fungal Endogenous Endophthalmitis

For patients with fungal endogenous endophthalmitis, intravitreal voriconazole (50-100ug/0.1ml) or amphotericin-B(5-10ug/0.1ml) are the commonly used antifungal drugs.⁵² Intravitreal voriconazole appears to be nontoxic up to doses of 100 μg and may be less toxic to the retina than intravitreal amphotericin B.⁵¹ However, intravitreal Amphotericin B (5 microgram/0.1ml) has been seen to be more effective against Candida infection^.53 This dose can be repeated after intervals of 48 h or more if there is evidence of persistent intraocular infection. Usually daily monitoring is done to look for response to the treatment.

Tables 6 and 7 summarise the commonly used drugs for endogenous endophthalmitis.

Role of Corticosteroids

There are no clear guidelines for the use of corticosteroids in endogenous endophthalmitis. Jackson et al. in their two case series, have reported better visual outcomes in the patients who received additional treatment with intraocular steroids.^2,4 On the other hand Shuwan lee et al. reported no significant association of the use of systemic steroids with better visual outcomes.⁵⁴

Intravitreal corticosteroids (e.g., dexamethasone 400 μg) by decreasing inflammation, may play a role of an adjunct in some patients with bacterial endophthalmitis.⁵⁵ Generally, corticosteroids should be withheld until proper antimicrobials have been initiated, especially in patients with suspected fungal disease.

Surgical Treatment

For the treatment of endogenous endophthalmitis, pars plana vitrectomy is a commonly used modality. It is recommended for patients with severe and vision-threatening Candida, Aspergillus, or bacterial endophthalmitis.^{16,38, 56} It serves a dual role of diagnostic as well as a therapeutic intervention. It provides a good amount of samples for cultures and sensitivity and also reduces the load of infectious microorganisms in the vitreous cavity.

Pars Plana Vitrectomy comes with its own set of disadvantages which include surgical risks, such as retinal detachment, choroidal detachment, or sclerotomy site leakage. However, in the era of micro incision vitrectomy surgery the risk of complications has drastically reduced.

One large series reported improved outcomes in patients treated with pars plana vitrectomy.² Zhang et al. have also reported better visual outcomes in cases that underwent early vitrectomy.¹¹ Decision of doing an early vitrectomy has also been associated with a decrease in incidence of adverse outcomes like retinal detachment and evisceration or enucleation.^57,60 Sato et al. recommended the use of pars plana vitrectomy for Candida Endogenous Endophthalmitis before stage IV according to Ishibashi’s classification^.59 In cases of bacterial Endogenous Endophthalmitis, vitrectomy is generally performed when there is no response to intravitreal antibiotics within 48 h or when the eye condition continues to decline or with a worse grade of RAPD.⁴⁹ Yoon et al. and Ishii et al. suggested that in patients with Klebsiella endophthalmitis aggressive treatment including vitrectomy might lead to better final outcomes.^60-61

Prognosis

Endogenous endophthalmitis can result in poor visual prognosis and sometimes complete loss of vision if the treatment is delayed due to a missed diagnosis early in the course of management.²⁰ In one of the studies, a timely diagnosis and treatment have shown that 64 % of patients having visual acuity of counting fingers (CF) or better.²¹ Hence, the clinician has to maintain a very high level of suspicion when a patient with possible risk factors for endogenous endophthalmitis presents with decreased vision and vitreoretinal changes. As a prompt diagnosis and appropriate treatment can salvage some useful vision in such patients.

References:

1. Smith SR, Kroll AJ, Lou PL, Ryan EA. Endogenous bacterial and fungal endophthalmitis. Int Ophthalmol Clin 2007;47(2):173–83.
2. Jackson TL, Eykyn SJ, Graham EM, et al. Endogenous bacterial endophthalmitis: a 17-year prospective series and review of 267 reported cases. Surv Ophthalmol. 2003;48:403Y423.
3. A. E. Kuryian, S. G. Schwartz, J. L. Davis, and H. W. Flynn, “Endogenous endophthalmitis: bacterial and fungal,” in SriniVas Sadda, Ryan’s Retina, pp. 1700–1708, Elsevier, Amsterdam, Netherlands, 6th edition, 2017.
4. T. L. Jackson, T. Paraskevopoulos, and I. Georgalas, “Systematic review of 342 cases of endogenous bacterial endophthalmitis,” Survey of Ophthalmology, vol. 59, no. 6, pp. 627–635, 2014.
5. T. Nishida, K. Ishida, and Y. Niwa, “An eleven-year retrospective study of endogenous bacterial endophthalmitis,” Journal of Ophthalmology, vol. 2015, Article ID 261310, 2015.
6. D. Ratra, K. Saurabh, D. Das et al., “Endogenous endophthalmitis,” Asia-Pacific Journal of Ophthalmology, vol. 4, no. 5, pp. 286–292, 2015.
7. V. P. Dave, A. Pathengay, and B. Panchal, “Clinical presentations, microbiology and management outcomes of culture proven endogenous endophthalmitis in India,” Indian Journal of Ophthalmology, vol. 68, pp. 834–839, 2020.
8. E. T. Cunningham, H. W. Flynn, N. Relhan, and M. Zierhut, “Endogenous endophthalmitis,” Ocular Immunology & Inflammation, vol. 26, no. 4, pp. 491–495, 2018.
9. Y.-J. Chen, H.-K. Kuo, P.-C. Wu et al., “A 10-year comparison of endogenous endophthalmitis outcomes: an East Asian experience with Klebsiella pneumoniae infection,” Retina, vol. 24, no. 3, pp. 383–390, 2004.
10. J. Wong, T. K. Chan, H. M. Lee, and S. P. Chee, “Endogenous bacterial endophthalmitis an East Asian experience and a reappraisal of a severe ocular affliction,” Ophthalmology, vol. 107, no. 8, pp. 1483–1491, 2000.
11. Agarwal M, Sachdeva M, Pal S, Shah H, Kumar R M, Banker A. Endogenous endophthalmitis a complication of COVID-19 pandemic: a case series. Ocular immunology and inflammation. 2021 May 19;29(4):726-9.
12. Zhang YQ, Wishi WJ (2005) Treatment outcomes after pars plana vitrectomy for endogenous endophthalmitis. Retina 25(6):746–750
13. Sharma S, Padhi TR, Basu S, Kar S, Roy A, Das T (2014) Endophthalmitis patients seen in a tertiary eye care centre in Odisha: a clinicomicrobiological analysis. Indian J Med Res 139(1):91–98
14. Lim HW, Shin JW, Cho HY, Kim HK, Kang SW, Song SJ, Yu HG, Oh JR, Kim JS, Moon SW, Chae JB, Park TK, Song Y (2014) Endogenous endophthalmitis in the Korean population: a six-year retrospective study. Retina 34(3):592–602.doi:10.1097/IAE.0b013e3182a2e705
15. Ness T, Pelz K, Hansen LL. Endogenous endophthalmitis: microorganisms, disposition and prognosis. Acta Ophthalmol Scand 2007;85(8):852–6.
16. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal endophthalmitis: causative organisms, management strategies, and visual acuity outcomes. Am J Ophthalmol 2012;153(1):162–6.
17. Connell PP, O’Neill EC, Amirul Islam FM, et al. Endogenous endophthalmitis associated with intravenous drug abuse: seven year experience at a tertiary referral center. Retina 2010;30(10):1721–5.
18. Bross J, Talbot GH, Maislin G, Hurwitz S, Strom BL. Risk factors for nosocomial candidemia: a case-control study in adults without leukemia. Am J Med 1989;87(6):614–20.
19. Sridhar J, Flynn HW Jr, Kuriyan AE, Miller D, AlbiniT. Endogenous fungal endophthalmitis: risk factors, clinical features, and treatment outcomes in mold and yeast infections. J Ophthalmic Inflamm Infect. 2013;3(1):60.
20. Wu ZH, Chan RP, Luk FO, Liu DT, Chan CK, Lam DS, Lai TY (2012) Review of clinical features, microbiological spectrum, and treatment outcomes of endogenous endophthalmitis over an 8-year period. J Ophthalmol 2012:265078. doi:10.1155/2012/265078
21. Yonekawa Y, Chan RV, Reddy AK, Pieroni CG, Lee TC, Lee S (2011) Early intravitreal treatment of endogenous bacterial endophthalmitis. Clin Experiment Ophthalmol 39(8):771–778. doi:10.1111/j.1442-9071.2011.02545.x
22. Grixti A, Sadri M, Datta AV (2012) Uncommon ophthalmologic disorders in intensive care unit patients. Journal of critical care 27(6):746. doi:10.1016/j.jcrc.2012.07.013, e749-722
23. Dua S, Chalermskulrat W, Miller MB, Landers M, Aris RM (2006) Bilateral hematogenous Pseudomonas aeruginosa endophthalmitis after lung transplantation. Am J Transplant 6(1):219–224. doi:10.1111/j.1600-6143.2005.01133.x
24. Khan A, Okhravi N, Lightman S (2002) The eye in systemic sepsis. Clin Med 2(5):444–448
25. Nagao M, Saito T, Doi S, et al. Clinical characteristics and risk factors of ocular candidiasis. Diagn Microbiol Infect Dis 2012;73(2):149–52.
26. Kaburaki T, Takamoto M, Araki F, et al. Endogenous Candida albicans infection causing subretinal abscess. Int Ophthalmol 2010;30(2):203–6.
27. Weishaar PD, Flynn HW Jr, Murray TG, et al. Endogenous Aspergillus endophthalmitis: clinical features and treatment outcomes. Ophthalmology 1998;105(1):57–65.
28. Jampol LM, Dyckman S, Maniates V, Tso M, Daily M, O’Grady R. Retinal and choroidal infarction from Aspergillus: clinical diagnosis and clinicopathologic correlations. Trans Am Ophthalmol Soc 1988;86:422–40.
29. Georgala A, Layeux B, Kwan J, et al. Inaugural bilateral Aspergillus endophthalmitis in a seriously immunocompromised patient. Mycoses 2011;54(5):e631–3.
30. Rodrigues IA, Jackson TL (2014) A high-definition view of endogenous fungal endophthalmitis. The Lancet Infect Dis 14(4):358. doi:10.1016/S1473-3099(13)70216-0
31. Adam CR, Sigler EJ (2014) Multimodal imaging findings in endogenous Aspergillus endophthalmitis. Retina 34(9):1914–1915. doi:10.1097/IAE.0000000000000135
32. Cho M, Khanifar AA, Chan RV (2011) Spectral-domain optical coherence tomography of endogenous fungal endophthalmitis. Retin Cases Brief Rep 5(2):136–140. doi:10.1097/ICB.0b013e3181cc2146.
33. Griffin JR, Pettit TH, Fishman LS, Foos RY. Blood-borne Candida endophthalmitis: a clinical and pathologic study of 21 cases. Arch Ophthalmol 1973;89(6):450–6.
34. Roney P, Barr CC, Chun CO, Raff MJ. Endogenous aspergillus endophthalmitis. Rev Infect Dis 1986;8(6):955–8.
35. Lewis H, Aaberg TM, Fary DR, Stevens TS. Latent disseminated blastomycosis with choroidal involvement. Arch Ophthalmol 1988;106(4):527–30.
36. Blumenkranz MS, Stevens DA. Endogenous coccidioidal endophthalmitis. Ophthalmology 1980;87(10):974–84.
37. Chhablani J (2011) Fungal endophthalmitis. Expert Rev Anti Infect Ther 9(12):1191–1201. doi:10.1586/eri.11.139
38. Tjpas PG, Kauffman CA, Andes D, Benjamin DK Jr, Calandra TF, Edwards JE Jr, Filler SG, Fisher JF, Kullberg BJ, Ostrosky-Zeichner L, Reboli AC, Rex JH, Walsh TJ, Sobel JD, Infectious Diseases Society of A (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48(5):503–535. doi:10.1086/596757
39. Hamada Y, Okuma R, Katori Y, Takahashi S, Hirayama T, Ichibe Y, Kuroyama M (2013) Bibliographical investigation (domestic and overseas) on the treatment of endogenous Candida endophthalmitis over an 11-year period. Med Mycol J 54(1):53–67
40. Christmas NJ, Smiddy WE. Vitrectomy and systemic fluconazole for treatment of endogenous fungal endophthalmitis. Ophthalmic Surg Lasers 1996;27(12):1012–18.
41. Wan WL, Kuhak BM, Smith MD, Oster HA, Luttrull KJ. Treatment of ocular fungal infections with oral fluconazole. Am J Ophthalmol 1995;119(4):477–81.
42. Urbak S, Degn T. Fluconazole in the management of fungal ocular infections. Ophthalmologica 1994;208(3):147–56.
43. Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994;330(4):263–72.
44. Edwards JE Jr, Bodey GP, Bowden RA, et al. International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis 1997;25(1):43–59.
45. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis 2004;38(2):161–89.
46. Scott LJ, Simpson D. Voriconazole: a review of its use in the management of invasive fungal infections. Drugs 2007;67(2): 269–98.
47. Hariprasad SM, Mieler WF, Holz ER, et al. Determination of vitreous, aqueous, and plasma concentration of orally administered voriconazole in humans. Arch Ophthalmol 2004;122(1):42–7.
48. Tsai AS, Lee SY, Jap AH (2010) An unusual case of recurrent endogenous Klebsiella endophthalmitis. Eye (London, England) 24(10):1630–1631.doi:10.1038/eye.2010.95
49. Ang M, Jap A, Chee SP (2011) Prognostic factors and outcomes in endogenous Klebsiella pneumoniae endophthalmitis. Am J Ophthalmol 151(2):338–344. doi:10.1016/j.ajo.2010.08.036, e332
50. Sharma S, Padhi TR, Basu S, Kar S, Roy A, Das T (2014) Endophthalmitis patients seen in a tertiary eye care centre in Odisha: a clinicomicrobiological analysis. Indian J Med Res 139(1):91–98
51. Espinel-Ingroff A, Boyle K, Sheehan DJ (2001) In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia 150(3):101–115
52. Sadiq MA, Hassan M, Agarwal A, Sarwar S, Toufeeq S, Soliman MK, Hanout M, Sepah YJ, Do DV, Nguyen QD. Endogenous endophthalmitis: diagnosis, management, and prognosis. J Ophthalmic Inflamm Infect. 2015 Dec;5(1):32. doi: 10.1186/s12348-015-0063-y. Epub 2015 Nov 3. PMID: 26525563; PMCID: PMC4630262.
53. Brod RD, Flynn HW Jr, Clarkson JG, Pflugfelder SC, Culbertson WW, Miller D. Endogenous Candida endophthalmitis: management without intravenous amphotericin B. Ophthalmology 1990;97(5):666–74.
54. Lee S, Um T, Joe SG, Hwang JU, Kim JG, Yoon YH, Lee JY (2012) Changes in the clinical features and prognostic factors of endogenous endophthalmitis: fifteen years of clinical experience in Korea. Retina 32(5):977–984. doi:10.1097/IAE.0b013e318228e312
55. Schulman JA, Peyman GA. Intravitreal corticosteroids as an adjunct in the treatment of bacterial and fungal endophthalmitis: a review. Retina 1992;12(4):336–40.
56. Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, Morrison VA, Segal BH, Steinbach WJ, Stevens DA, van Burik JA, Wingard JR, Patterson TF, Infectious Diseases Society of A (2008) Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 46(3):327–360. doi:10.1086/525258
57. Lim HW, Shin JW, Cho HY, Kim HK, Kang SW, Song SJ, Yu HG, Oh JR, Kim JS, Moon SW, Chae JB, Park TK, Song Y (2014) Endogenous endophthalmitis in the Korean population: a six-year retrospective study. Retina 34(3):592–602. doi:10.1097/IAE.0b013e3182a2e705
58. Sallam A, Taylor SR, Khan A, McCluskey P, Lynn WA, Manku K, Pacheco PA, Lightman S (2012) Factors determining visual outcome in endogenous Candida endophthalmitis. Retina 32(6):1129–1134. doi:10.1097/IAE.0b013e31822d3a34
59. Sato Y, Miyasaka S, Shimada H (2001) Prognosis of endogenous fungal endophthalmitis and utility of Ishibashi’s classification. Jpn J Ophthalmol 45(2):181–186
60. Yoon YH, Lee SU, Sohn JH, Lee SE (2003) Result of early vitrectomy for endogenous Klebsiella pneumoniae endophthalmitis. Retina 23(3):366–370
61. Ishii K, Hiraoka T, Kaji Y, Sakata N, Motoyama Y, Oshika T (2011) Successful treatment of endogenous Klebsiella pneumoniae endophthalmitis: a case report. Int Ophthalmol 31(1):29–31. doi:10.1007/s10792-010-9387-7
62. Chee SP, Jap A. Endogenous endophthalmitis. Current opinion in ophthalmology. 2001 Dec 1;12(6):464-70.
63. Ajay E. Kuriyan, Stephen G. Schwartz, Janet L. Davis, Harry W. Flynn Jr. Endogenous Endophthalmitis: Bacterial and Fungal. Ryans’s Retina 6^th Edition, edited by Andrew p. Schachat Elsevier Inc. 2018,1700-1708
64. Shah, Kunal K; Venkatramani, Devendra,; Majumder, Parthopratim Dutta1 A case series of presumed fungal endogenous endophthalmitis in post COVID-19 patients, Indian Journal of Ophthalmology: May 2021 - Volume 69 - Issue 5 - p 1322-1325 doi: 10.4103/ijo.IJO_3755_20
65. Shroff, Daraius,; Narula, Ritesh1; Atri, Neelam; Chakravarti, Arindam1; Gandhi, Arpan2; Sapra, Neelam3; Bhatia, Gagan; Pawar, Shraddha R1; Narain, Shishir Endogenous fungal endophthalmitis following intensive corticosteroid therapy in severe COVID-19 disease, Indian Journal of Ophthalmology: July 2021 - Volume 69 - Issue 7 - p 1909-1914 doi: 10.4103/ijo.IJO_592_21