Actinomycosis in Ophthalmology 

The bacterial order Actinomycetales comprises 3 families: Actinomycetaceae, Mycobacteriaceae, and Streptomycetaceae. The genus Actinomyces, a member of the family Actinomycetaceae, grows as a fragile branching filament that tends to fragment into bacillary and coccoid forms producing chains of either conidia or arthrospores.[1, 2]

Actinomyces israelii. (The image is labeled.)

Actinomyces israelii species is a gram-positive, cast-forming, non–acid-fast, non–spore-forming anaerobic bacillus that is difficult to isolate and identify.

Actinomyces israelii (non–spore-forming, gram-positive bacilli). Courtesy of Medical Education Information Center, Department of Pathology and Laboratory Medicine, The University of Texas-Houston Medical School.

Its filamentous growth and mycelialike colonies have a striking resemblance to fungi. They are soil organisms, often found in decaying organic matter (eg, wet hay, straw). It is primarily a commensal microbe found in normal oral cavities, in tonsillar crypts, in dental plaques, and in carious teeth.[3, 4, 5, 6]

Keratitis

Most reported cases of Actinomyces keratitis (keratoactinomycosis) are caused by A israelii. It is characterized by a dry ulceration with central necrosis, surrounded by a gutter of demarcation, usually accompanied by iritis and hypopyon. In severe cases, descemetocele and perforation may occur.

A primary corneal ulcer attributable to Actinomyces species is rare and usually follows corneal trauma.[7] A rare case of keratoactinomycosis developing in the absence of any known ocular trauma was reported in Kuala Lumpur.

Canaliculitis

Primary chronic canaliculitis is an uncommon problem caused by A israelii (Streptothrix).

McKellar presented a 10-year-old girl with a 6-month history of intermittent conjunctivitis and discharge from her pouted left lower punctum. Topical treatment with chloramphenicol/polymyxin sulphate failed despite a diagnosis of probable A israelii infection confirmed by microbiology. Surgical exploration revealed a canalicular diverticulum and 3 canaliculiths demonstrating solid casts of Actinomycetes on histologic examination. A therapeutic triad of punctoplasty, cast removal, and adjunctive topical cefazolin resulted in resolution.[8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20]

Other ocular involvement

Actinomycetes have been described as causative organisms in conjunctivitis, blepharitis, carunculitis, dacryocystitis, lacrimal gland ductulitis, crystalline keratopathy, postsurgical endophthalmitis, and infected porous orbital implant. Cervicofacial actinomycosis has also been reported.[21, 22, 23]

Postoperative endophthalmitis

Acute postoperative endophthalmitis caused by Actinomyces neuii after uncomplicated phacoemulsification with posterior chamber intraocular lens implant in a 58-year-old male has been reported. On postoperative day 6, he presented with pain, redness, and decreased visual acuity. Chronic endophthalmitis by Actinomyces neuii subspecies anitratus after uneventful phacoemulsification with implantation of a foldable posterior chamber intraocular lens in a 75-year-old man has been reported as well. Four weeks after surgery, anterior chamber and vitreous cellular debris developed in this eye.[24]

Endophthalmitis, attributable to Actinomyces viscosus, developed in a 78-year-old man after cataract surgery. Postoperative endophthalmitis with this organism is a rare occurrence. Inflammation was characterized by anterior segment and vitreous cellular debris in cases of chronic postoperative endophthalmitis associated with Actinomyces species.[25]

Actinomycosis may be the cause of endophthalmitis after anti-VEGF intravitreal injection.[26]

Endogenous endophthalmitis has been reported with Actinomyces israelii.[27]

Lacrimal Sac

Actinomycosis of the lacrimal sac may masquerade as a lacrimal sac malignancy.[28]

Orbital actinomycosis

Painful ophthalmoplegia resulting from orbital actinomycosis has been reported.[29, 30, 31, 32, 33, 34]

Frequency

United States

Primary chronic canaliculitis is an uncommon problem that can be overlooked; however, it may account for approximately 2% of all tearing problems. Actinomycosis may form in up to 2% of all lacrimal disease. Its occurrence is probably much less in other areas.

International

Actinomycosis occurs worldwide, with a likelihood for higher prevalence rates in areas with low socioeconomic status.

In a literature review of lacrimal canaliculitis presented by Freedman et al in 2011, the prevalence of Actinomyces species infection was 30.3%.[20]

Race

No racial predilection exists.

Sex

No sexual predisposition exists.

Age

Actinomycosis can affect people of all ages. No age predisposition exists.

History may be positive for the following:

• Keratitis

  • Symptoms

    • Progressive visual haze

    • Increasing ocular pain

    • Photophobia

    • Constant watering

    • Redness

  • Past ocular history

    • Corneal trauma, especially when contaminated by vegetable matter

    • Ongoing, nonresponsive treatment

  • Personal history - Outdoor laborer

• Canaliculitis

  • Symptoms[8, 9]

    • Chronic or recurrent conjunctivitis

    • Chronic mucopurulent discharge

    • Epiphora

    • Ocular surface irritation

    • Medial eyelid and canthal pain

    • Pouting punctum

    • Failure to resolve despite topical treatment

  • Past ocular history and medical history - Similar to keratitis

• Endophthalmitis

  • Symptoms

    • Blurring of vision

    • Floaters

    • Ocular pain

    • Redness

    • Tearing

  • Past ocular history

    • Uneventful phacoemulsification with implantation of a foldable posterior chamber intraocular lens

  • Personal history

    • Elderly

    • Debilitated

The following physical findings may be present:

• Keratitis

  • Gross observations

    • Some conjunctival congestion

    • Gray-white corneal lesion

  • Slit lamp findings

    • A dry ulceration with central necrosis, surrounded by a gutter of demarcation, usually accompanied by iritis, and hypopyon may be present.

    • Gray-white satellite stromal infiltrates adjacent to advancing edges may be present.

    • In severe cases, descemetocele and perforation may occur.

• Canaliculitis[8, 9]

  • Gross observations

    • Chronic discharge, swollen and pouted punctum

    • A pouted punctum is clinically diagnostic, although it occurs in less than 50% of all patients who are affected.

    • Typically, the discharge is particulate and contains concretions.

    • The plica may be swollen and congested, and canalicular swelling and overlying lid erythema are often present.

    • The lower lid is more commonly affected, and the lacrimal sac and the duct are usually not involved.

  • Slit lamp findings

    • Pouted punctum

    • Plica may be swollen and congested.

    • Particulate canalicular discharge with or without concretions

  • Images of canaliculitis

    Canaliculitis of the left lower lid. Courtesy of Peter Rubin, MD, Director, Eye Plastics Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School.
    Canaliculitis of the right upper lid. Courtesy of Peter Rubin, MD, Director, Eye Plastics Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School.
    A pediatric patient with canaliculitis. Courtesy of Peter Rubin, MD, Director, Eye Plastics Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School.

• Endophthalmitis

  • Gross observations

    • Conjunctival injection

    • Elevated tear meniscus

  • Slit lamp findings

    • Anterior chamber cells and flare

    • Hypopyon

    • Vitreous debris

Causes include the following:

• Infectious

  • Actinomyces species

  • See Background.

The following laboratory studies may be usefl:

• Canalicular discharge and canaliculiths

  • Gram stain/Giemsa stain

  • Cultures and sensitivities (ie, blood agar, Sabouraud, anaerobic)

  • Special stains (ie, calcofluor white)

• Smears and corneal scrapings

  • Ziehl-Neelsen stain

• Anterior chamber (aqueous fluid) aspirate

  • Gram stain/Giemsa stain

  • Cultures and sensitivities (ie, blood agar, Sabouraud, anaerobic)

• Vitreous samples

  • Gram stain/Giemsa stain

  • Cultures and sensitivities (ie, blood agar, Sabouraud, anaerobic)

  • Polymerase chain reaction

  • rRNA sequence analysis

The following imaging studies may be useful:

• Distension dacryocystography: Contrast material is used to visualize the anatomic details of the lacrimal drainage system.

• Scanning electron microscopy

• High-resolution ultrasound (transducer frequency of 20 MHz): The 20-MHz scanner images may reveal pathological findings that are invisible during a slit lamp examination. Ultrasonic images of chronic canaliculitis show ectasia of the canaliculus and sulfur grains measuring 1-2 mm in diameter.[35, 36, 37, 38]

• Brain and orbital CT scan may be of use in cases of painful ophthalmoplegia.

Probing may be performed with a lacrimal probe to check for a diverticulum and remaining casts.

Canaliculitis

• A 2-snip punctoplasty may be performed under anesthesia.

• Curettage may also be helpful in removing any adherent casts from the canaliculus.

• Subsequent lacrimal irrigation with 2 MU of penicillin in 20 mL of sterile water may be helpful.

Endophthalmitis

• A diagnostic and therapeutic, 3-port, pars plana vitrectomy may be performed in cases where a diagnosis has not been achieved.

Histologic examination of the canaliculiths demonstrated that they consisted of solid casts of Actinomycetes with typical branching and filamentous structures. The organisms were found by using a Gram stain on the histopathologic preparations and by using a scanning electron microscopy.

Electron microscopic results of an actinomycosis of the lacrimal canaliculus were presented in 1980. The interior of the actinomycotic conglomerate showed no evidence of a cellular defense reaction, but, in the loosely woven outer network of hyphae, a massive granulocytic reaction was observed to be present. After phagocytosis, the structure of the actinomycotic microorganisms within the granulocytes was not significantly damaged. Within the tissue of the lacrimal canaliculus, adjacent to the actinomycotic conglomerate, an increased number of plasma cells were observed to be present; however, no organisms were present.

Keratitis

Actinomycetes are usually susceptible to penicillins and cephalosporins.[39, 40, 41, 42] The treatment of keratoactinomycosis used to be excision of necrotic tissue, followed by cauterization. However, good results have been obtained by subconjunctival penicillin coadministered with systemic iodides. Alternatively, topical sulfacetamide or penicillin can be used.

Canaliculitis

Actinomycetes are usually susceptible to penicillins and cephalosporins. Postoperatively, patients may be treated with topical cefazolin for 1 month. Adjunctive hyperbaric oxygen therapy for actinomycotic lacrimal canaliculitis has been reported.[43]

Endophthalmitis

Intraocular, periocular, topical, and systemic therapy.

Keratitis

• All reported cases of keratoactinomycosis responded to therapy, which included intraocular, topical, and systemic antibiotics, as well as pars plana vitrectomy and partial iridectomy.
• Urgent keratoplasty for a corneal infection by Actinomyces species was reported in a 41-year-old man.

Canaliculitis

• Failure to resolve canaliculitis by using topical treatment requires surgical exploration of the canalicular system and removal of any casts.[8, 15] Extensive surgery is not always required.

• A 2-snip punctoplasty, cast removal, curettage, probing, and adjunctive antibiotic therapy usually result in resolution of the canaliculitis.

• Lee et al in 2009 presented a 1-snip punctoplasty and canalicular curettage. The affected punctum is incised along the posterior wall vertically. A chalazion curette is inserted into the canaliculus, and the concretions are evacuated.[44]

• Cultivation of the surgically obtained dacryoliths and secretion enables reliable proof of Actinomyces and allows for an appropriate therapy for canaliculitis. Even though Actinomyces species are sensitive to penicillin, cure of canaliculitis does not occur until all the concretions and the granulations that are present in the canaliculus are meticulously removed.

Endophthalmitis

A diagnostic and therapeutic, 3-port, pars plana vitrectomy may be performed in cases where a diagnosis has not been achieved.[25]

An external disease and cornea specialist may provide care for the anterior segment.

An oculoplastics consult may be required for eyelid and orbital involvement.

A posterior segment surgeon is necessary for endophthalmitis.

Actinomyces organisms are usually susceptible to penicillins and cephalosporins. Good results have been obtained by subconjunctival penicillin coadministered with systemic iodides. Alternatively, topical sulfacetamide or penicillin can be used.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Penicillin G (Pfizerpen)

Exerts bactericidal action against penicillin-susceptible microorganisms during the stage of active multiplication. Acts by inhibiting biosynthesis of cell wall mucopeptide, rendering the cell wall osmotically unstable. Not active against penicillinase-producing bacteria, which include many strains of staphylococci

Cefazolin (Ancef, Kefzol, Zolicef)

First-generation cephalosporin with excellent activity against gram-positive cocci, including penicillinase-producing Staphylococcus aureus, penicillinase-producing Staphylococcus epidermidis, group A beta-hemolytic streptococci (Streptococcus pyogenes), group B streptococci (Streptococcus agalactiae), and Streptococcus pneumoniae. Ineffective against Bacteroides fragilis and only weak activity against gram-negative organisms.

Class Summary

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Sulfacetamide ophthalmic (Sulamyd, Bleph-10)

N-acetyl-substituted derivative; at 30% solution, topical sulfacetamide has pH of 7.4 and has good tissue penetration.

Patients should receive follow-up care as needed.

Postoperatively, patients may be treated with topical cefazolin for 1 month.

Prognosis is excellent once the organism is positively identified and appropriately treated.

Patients should be advised to wear protective eye gear when working with vegetable matter.