255 ANOPHTHALMOS 743.00

Nick Mamalis, MD

Salt Lake City, Utah

Brian A. Hunter, MD

Salt Lake City, Utah

ETIOLOGY/INCIDENCE

True or primary anophthalmos is very rare and occurs when the neuroectoderm of the primary optic vesicle fails to develop from the anterior neural plate of the neural tube during embryologic development. The diagnosis of true anophthalmos can be made only with complete absence of ocular tissue within the orbit. Secondary anophthalmos refers to the failure of the optic vesicle to form in the presence of anatomic malformations within the ventral forebrain. More commonly, children who are born with a unilaterally small orbit and no visible eye have a very small or microphthalmic globe present within the orbital soft tissue. Microphthalmos can occur due to a problem in the development of the globe at various stages of growth of the optic vesicle. The presence of an eye is necessary in utero to stimulate growth of the orbit, lids, and ocular fornices. A child born with anophthalmia commonly has a small orbit with narrowed palpebral fissure and a shrunken fornix.

●Prevalence range 0.3 to 1.9 per 10,000 live births.

●Idiopathic/sporadic or inherited (recessive, dominant, or sex linked).

●Trisomy 9, 13 through 15.

●Gene deletions chromosome 3, 7, 14. Deletions involving SOX2 and SIX6.

●Gene rearrangements (balanced de novo translocations) 46 XXt(1;2)(p31.2;q23); 46 XY (t8;12)(q22;q21); 46,XX, t(3;11).

●Prenatal exposures to TORCH infections (toxoplasmosis, rubella, cytomegalovirus, herpes) as well as alcohol, thalidomide, retinoic acid, hydantoin, and lysergic acid diethylamide (LSD).

●Syndromes associated with abnormalities of the CNS, genitourinary system, and in association with limb anomalies (i.e. SOX2, anopthalmia-oesophageal-genital syndrome (AEG), oligodactyly-ophthalmo-acromelic syndrome (OAS); micropthalmia-anaopthalmia-coloboma (MAC); Waardenburg anophthalmia syndrome (WAS), Lenz syndrome XLR).

●Associated with multiple syndromes with hemifacial microsomia and other craniofacial malformations (i.e. Goldenhar’s syndrome, Hallermann–Streiff syndrome).

COURSE/PROGNOSIS

●True anophthalmos is a pediatric ocular emergency.

●The growth and development of the bony orbit are correlated with the growth of the globe.

●The lack of an eye or a microphthalmic eye prevents the orbit from developing properly.

●A small bony orbital cavity results not only in a cosmetic deformity but also does not allow for proper fitting of a prosthesis.

●Anophthalmos may be unilateral or bilateral.

DIAGNOSIS

Clinical signs and symptoms

Orbital

●Reduced size of the bony orbital cavity.

●Small orbital rim.

●Small or maldeveloped optic foramen.

●Lacrimal gland and ducts may be absent.

●Extraocular muscles usually absent.

Eyelids

●Microblepharism: a foreshortening of the eyelids in all directions.

●Contraction of the orbicularis oculi muscle.

●Absent or decreased levator function and lid folds.

●Shallowing of the inferior conjunctival fornix.

Globe

●Completely absent in primary anophthalmos.

●Very small, malformed globe in microphthalmos.

Laboratory findings

●On computed tomography scanning and magnetic resonance imaging, patients with bilateral anophthalmos often have an associated absence of the optic chiasm, diminished size of the posterior optic pathways, and agenesis or dysgenesis of the corpus callosum.

●Ultrasound imaging using B-scan showing complete absence of ocular tissue in anophthalmos. A-scan shows decreased axial length in microphthalmos. Transvaginal ultrasound can detect eye malformations after 22 weeks gestation; however, the sensitivity for use in detecting anopthalmia is not known.

●Patients with unilateral anophthalmos often have severe craniofacial anomalies.

Globe • 22 SECTION

Acute bacterial endophthalmitis is a serious and vision-threat- ening intraocular infection that requires emergent treatment. The Endophthalmitis Vitrectomy Study (EVS) was a landmark study that evaluated the roles of immediate vitrectomy and systemic antibiotics in the treatment of acute post-cataract extraction endophthalmitis. Injection of intravitreal antibiotics is the mainstay of treatment for exogenous endophthalmitis. Systemic treatment and occasionally vitrectomy and intravitreal antibiotics are required for endogenous endophthalmitis. Prophylaxis of postoperative endophthalmitis remains a controversial issue, and current recommendations include lid scrubs, use of povidone-iodine in the conjunctival fornices, and adequate aseptic technique.

ETIOLOGY/INCIDENCE

Bacterial endophthalmitis is classified based on the route of infection as either exogenous or endogenous. Exogenous endophthalmitis can occur following intraocular surgery, penetrating injury, or less commonly from microbial keratitis, scleritis, or an infected scleral buckle. A recent development is the occurrence of exogenous endophthalmitis following intravitreal injections of steroids or other drugs. The incidence of postoperative endophthalmitis has been reported to be:

●0.07% to 0.12% after routine cataract surgery;

●0.36% after secondary intraocular lens placement;

●0.17% after penetrating keratoplasty;

●0.06% to 1.8% after glaucoma filtering surgery.

Incidence of bleb-related endophthalmitis is greater with the use of antifibrotics because of thinner blebs, and with inferiorly located blebs presumably because of greater exposure of the bleb to bacteria-laden tear film in this location. The causative organisms in postoperative endophthalmitis are usually part of the normal ocular bacterial flora. The incidence of endophthalmitis after penetrating trauma is approximately 7%, greater in the presence of an intraocular foreign body (9% to 11%) and can be as high as 30% in the setting of rural penetrating trauma. The incidence of intravitreal injection-related endophthalmitis after triamcinolone injections is between 0.0% and 0.87%, and after ganciclovir injections is up to 0.6%. Endogenous endophthalmitis, also called metastatic endophthalmitis, occurs by hematogenous spread of the organism in patients with sepsis, immunosuppression, or intravenous drug use. Endogenous endophthalmitis is less common and accounts for 2–6% of all cases of bacterial endophthalmitis.

COURSE/PROGNOSIS

The course and prognosis depend on:

●The type of endophthalmitis;

●Duration of time to presentation and treatment;

●Virulence of the organism.

The prognosis for achieving good final visual acuity has increased substantially with the introduction of intravitreal antibiotics. Prior to the introduction of intravitreal antibiotics, intravenous and topical antibiotics were administered and, in a survey of cases from the years 1944–1966, 73% had final vision of hand motions or worse. In the EVS, which evaluated cases of acute postoperative endophthalmitis, at 9 to 12 months

after treatment, 53% of eyes had a visual acuity of 20/40 or better, 74% had visual acuity of 20/100 or better, 15% had visual acuity of 5/200 or worse, and 5% had no light perception (LP). The most important risk factor for poor visual outcome in the EVS was an initial visual acuity of light perception (LP) only, with only 23% of patients with LP achieving 20/40 or better vision compared with 64% of patients presenting with better than LP vision. Other factors associated with poor outcome included:

●Small pupil size after maximal dilation;

●Absence of a red reflex;

●Presence of rubeosis irides;

●Findings of an afferent papillary defect;

●Corneal infiltrate or ring ulcer;

●Abnormal intraocular pressure;

●Poor media clarity with inability to distinguish any retinal vessels;

●Type of organism grown in culture.

The leading cause of final vision less than 20/40 was an abnormality of the macula.

The prognosis for retaining good vision is generally better in cases that are culture-negative or culture-positive for coagulasenegative staphylococci, and in cases of chronic or delayed-onset endophthalmitis, i.e. those presenting 6 weeks after cataract surgery. However, the prognosis for patients with bleb-associ- ated, post-traumatic, and endogenous endophthalmitis is generally worse than for patients with acute postoperative endophthalmitis. In bleb-associated endophthalmitis, infection with more virulent organisms is more frequent, and pre-exist- ing glaucoma may limit final vision. Post-traumatic endophthalmitis is associated with a poor visual prognosis with approximately 30% of patients achieving visual acuity better than 20/400. Cases associated with Bacillus cereus or with rural trauma portend an especially poor prognosis. Traumainduced changes may also directly affect the final outcome. Poor prognosis in endogenous endophthalmitis has been attributed to delay in diagnosis, diffuse infection (panophthalmitis), and infection with virulent and in particular,gram-negative organisms. Pooled analysis of cases reported between 1976 and 1985 showed that only 41% of patients had counting fingers (CF) or better vision, 26% had no light perception, and 29% required evisceration, a trend that has remained unchanged in analyses since 1986. In addition, a 5% mortality rate due to extraocular spread of infection has been reported.

DIAGNOSIS

The diagnosis of endophthalmitis is usually made on clinical grounds. Vitreous inflammation greater than expected is the key diagnostic finding that should lead to the suspicion of endophthalmitis.

Clinical signs and symptoms

●Acute postoperative endophthalmitis.

Presenting symptoms in the EVS

●Decreased vision.

●Pain.

●Red eye.

●Swollen lid.

●Hypopyon.

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Examination findings revealed

●Visual acuity less than 5/200 (86%).

●Light perception (26%).

●Hypopyon (86%).

●No retinal vessel visible by indirect ophthalmoscopy (79%).

●Afferent pupillary defect (12%).

●Corneal wound abnormality (5%).

●Corneal infiltrate or ring ulcer (5%).

While pain is generally considered a key presenting symptom, it should be noted that nearly a quarter of the patients in the EVS presented without pain. In addition, hypopyon was absent in 14% of the patients.

●Chronic postoperative endophthalmitis usually presents as an anterior uveitis weeks to months after the intraocular procedure. It may respond transiently to corticosteroid treatment. The presence of vitreous inflammation and posterior capsular opacities or plaques are highly suggestive of chronic endophthalmitis.

●Bleb-related endophthalmitis. Patients can present with bleb-related endophthalmitis months to years after glaucoma filtering surgery with symptoms of:

●Ocular pain;

●Redness;

●Decreased vision;

●Clinical signs.

●Bleb leak.

●Conjunctival injection and chemosis.

●Inflamed bleb.

●Hypopyon.

●Anterior and vitreal inflammation.

It is important to distinguish blebitis from bleb-related endophthalmitis because treatment methods are different for the two entities. When the inflammation is localized to the bleb with the absence of a hypopyon or vitreal inflammation, it is termed ‘blebitis.’

●Post-traumatic endophthalmitis. Patients with penetrating injuries and with intraocular foreign bodies may have intraocular inflammation and signs similar to acute postoperative endophthalmitis on presentation or after primary repair. Endophthalmitis is suspected mainly on clinical grounds in these cases.

●Intravitreal injection-related endophthalmitis. Patients may present with anterior and vitreal inflammation within one week of an intravitreal injection. Pseudo-endophthalmitis, presumably as a result of reaction to the concomitant vehicle or dispersion of steroid particles into the anterior chamber simulating a hypopyon, should be cautiously distinguished from endophthalmitis by the lack of significant decrease in vision, significant pain, and severe vitreal inflammation.

Laboratory findings

Microbiologic studies of vitreous and anterior chamber specimens obtained are recommended, mainly to determine the infectious organism and to direct treatment in the event of need for reinjection of intravitreal antibiotics. Bacterial endophthalmitis is a clinical diagnosis, and empiric treatment with broadspectrum antibiotics is initiated emergently well before microbiology results become available. In addition, the rate of culture-negative vitreous samples, whether or not a vitrectomy is performed, is approximately 30%. Gram stain, aerobic and anaerobic cultures are routinely obtained. Based on findings of

the EVS, gram stain results should not be used solely in determining the choice of antibiotics in the treatment of endophthalmitis, and vitrectomy does not result in a greater rate of culture-positive specimens. Cultures of conjunctiva or cornea may theoretically have a role in post-traumatic endophthalmitis cases, but are not expected to add information when aqueous and vitreal samples are obtained. Patients with endogenous endophthalmitis should have a work-up for infectious diseases to identify an extraocular focus of infection. This should include cultures of blood and urine as well as evaluation of indwelling intravenous lines, and other studies determined by history and physical findings. In reported series of endogenous endophthalmitis, blood cultures were more likely to be positive than vitreous cultures. However, in the absence of positive cultures from extraocular studies, aqueous and vitreal cultures are recommended to aid in diagnosis.

The microbial spectrum in the different types of endophthalmitis is as follows:

●Acute postoperative (EVS):

●Gram-positive coagulase-negative micrococci (mostly

Staphylococcus epidermidis) (70%);

●Other gram-positive (24.2%);

●Staphylococcus aureus (9.9%);

●Streptococcus (9%);

●Enterococcus (2.2%);

●Miscellaneous (3.1%).

●Chronic postoperative endophthalmitis:

●Gram-positive coagulase-negative micrococci, mostly

Staphylococcus epidermidis;

●Other gram-positive organisms, Staphylococcus aureus,

Streptococcus spp.;

●Propionibacterium acnes;

●Corynebacterium spp.;

●Actinomyces spp.;

●Nocardia;

●Fungi.

●Bleb-related endophthalmitis:

●Staphylococcus spp., Streptococcus spp.;

●Haemophilus influenzae;

●Enterococcus spp.;

●Fastidious gram-negative rods;

●Pseudomona aeruginosa.

●Post-traumatic endophthalmitis:

●Coagulase-negative Staphylococci spp.;

●Staphylococcus aureus, Streptococcus spp.;

●Bacillus cereus;

●Propionibacterium acnes;

●Fungi;

●Others.

●Endogenous endophthalmitis: gram-positive organisms, mainly:

●Streptococcus pneumoniae;

●Staphylococcus aureus;

●Group A and group B Streptococci;

●Bacillus ceres.

Gram-negative organisms:

●Klebsiella spp.;

●E. coli;

●Pseudomonas spp.;

●N. meningitides;

●Serratia marcescens;

●Listeria monocytogenes;

●N. asteroids.

●Intravitreal injection-related endophthalmitis:

●Gram-positive coagulase-negative Staphylococcus spp.;

●Streptococcus spp.;

●Mycobacterium chelonae.

Differential diagnosis

●Acute postoperative endophthalmitis:

●Phacoanaphylactic endophthalmitis, a granulomatous inflammation with keratic precipitates as a result of immune reaction to lens proteins;

●Aseptic endophthalmitis, a severe sterile uveitis that may present with a hypopyon and mild vitreous inflammation. Pain and progressive vision loss are not characteristic. This condition usually resolves with topical steroid treatment.

●Chronic postoperative endophthalmitis:

●Pre-existing uveitis;

●Sterile inflammation attributed to reaction to contaminants on the intraocular lens, such as polishing compounds;

●Rebound inflammation related to abrupt discontinuation of steroid drops;

●Iris or vitreous incarceration in the wound, resulting in a low-grade inflammation;

●Uveitis-glaucoma-hyphema syndrome;

●Fungal endophthalmitis.

●Bleb-related endophthalmitis:

●Blebitis, presenting classically as ‘white on red,’ with the bleb appearing white against inflamed conjunctiva;

●Anterior uveitis;

●Uveitis-glaucoma-hyphema syndrome.

●Post-traumatic endophthalmitis:

●Phacoanaphylactic endophthalmitis;

●Sterile inflammatory reaction to uveal incarceration or intraocular foreign body;

●Sympathetic ophthalmia with bilateral anterior uveitis with keratic precipitates, vitreous inflammation, presence of depigmented nodules (Dalen–Fuchs’ nodules) at the level of the retinal pigment epithelium, and choroidal thickening on B-scan ultrasonography.

●Endogenous endophthalmitis:

●Non-infectious anterior uveitis;

●Fungal endophthalmitis;

●Intraocular lymphoma;

●Retinoblastoma in children.

●Intravitreal injection-related endophthalmitis:

●‘Pseudo-endophthalmitis,’ or non-infectious endophthalmitis, seen after intravitreal triamcinolone injection, presumably as a result of toxic or inflammatory reaction to the drug, the vehicle in which the drug is suspended, or a contaminant in the preparation. This condition is seen in the immediate post-injection period, typically within two days. The presenting signs of hypopyon, anterior and vitreal inflammation, and decreased vision make it difficult to distinguish this entity from infectious endophthalmitis. With observation, the inflammation resolves within one week.

PROPHYLAXIS

Preoperative and intraoperative preventive measures have been proposed and employed in an attempt to decrease the incidence of endophthalmitis. Since the source of organisms in postopera-

tive endophthalmitis is most commonly the patient’s ocular flora, the goal is to reduce the bacterial load and treat any external eye disease prior to operating. An evidence-based assessment of bacterial endophthalmitis prophylaxis found that several measures have been considered, including preoperative povidone-iodine, lash trimming, saline irrigation, topical antibiotics, antibiotic-containing irrigating solutions, and postoperative subconjunctival antibiotics. The use of preoperative povidone-iodine received the strongest recommendation.

Preoperative measures include:

●Treatment of blepharitis, conjunctivitis, dacryocystitis, and periocular infections;

●Use of adequate aseptic techniques with sterile preparation of eyelashes, eyelids, and periocular skin, and draping of eyelashes and lid margins;

●5% povidone-iodine solution instilled in the conjunctival fornices;

●Topical preoperative antibiotics, which are widely used and theoretically lead to decreased bacterial load on the ocular surface. Some antibiotics, such as fluoroquinolones, may have adequate aqueous penetration. However, despite these theoretical considerations and routine use, clinical studies are yet to demonstrate their efficacy in preventing endophthalmitis.

Intraoperative measures include:

●Use of meticulous aseptic technique;

●Avoidance of placement of intraocular lens on the ocular surface prior to introduction into the eye;

●Use of heparin surface-modified intraocular lenses, based on demonstration of decreased bacterial adherence in vitro. The use of low molecular weight heparin in the irrigating fluid failed to demonstrate a statistically significant reduction in the rate of culture-positive anterior chamber aspirates;

●Placement of a 10-0 nylon suture in the incisional wound if there is capsular rupture, vitreous loss, or any concern about wound integrity. Recent evidence suggests an increased risk of postoperative endophthalmitis with sutureless corneal incisions; thus, a low threshold for placement of suture to avoid microleaks from the wound is recommended;

●Subconjunctival injection of antibiotics, which remains controversial. This method has been shown to reduce ocular flora more than topical antibiotics. However, in a retrospective 10-year review of the incidence of postoperative endophthalmitis, 23 out of 54 (42%) patients with culture-positive endophthalmitis had received prophylactic subconjunctival antibiotics at the end of their surgeries, and of these, 14 (61%) were sensitive to the antibiotics used. Subconjunctival gentamicin, in particular, should be avoided given the risk of irreversible macular infarction;

●Postoperative topical antibiotics, which are in routine use despite the lack of data proving their benefit in the prevention of endophthalmitis;

●Use of antibiotics in the irrigating fluid, not recommended by the authors. The Center for Disease Control and Prevention recommends against the routine use of vancomycin in the irrigating fluid given the risk of emerging vancomycin resistance. The use of aminoglycosides in the irrigating fluid should be avoided given the risk of macular toxicity from incorrect dilution of the antibiotic. Cases of endophthalmitis have been reported despite the use of this measure.

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