To reduce the cost and burden on both patients and providers, dropless cataract surgery uses a perioperative intracameral, transzonular, or intravitreal injection of antibiotic and steroid agents, reducing the need for postoperative eyedrops.1 Compounded combination injections include either 2 (triamcinolone–moxifloxacin) or 3 (triamcinolone–moxifloxacin–vancomycin) agents.1–3 Although seemingly an attractive option, perioperative injection of compounded antibiotics and corticosteroid remains controversial. Issues associated with such injections, including compounding errors, uncertain pharmacokinetics, antibiotic resistance, and steroid-induced ocular hypertension, have contributed to the slow adoption of dropless cataract surgery.3–5
Another concern of this procedure is the immunosuppression associated with intraocular injection of corticosteroids. Unlike drop regimens, where corticosteroids can be immediately stopped if a problem arises, intraocular injection administration allows long-acting steroids to remain in the eye for weeks.1,6 While reducing inflammation, the injection also creates a local immunocompromised environment, primed for opportunistic infections and other immune-mediated pathologies to manifest.6 Comorbid conditions such as previous infection and diabetes mellitus further suppress the immune system.7 Even months after corticosteroid injection, a patient might still be locally immunocompromised and susceptible to infection and other pathologies.7 In addition, unrecognized preoperative infections could be rendered worse with the intraoperative administration of a long-acting steroid.
In this case report, we describe 3 patients who, after having uneventful dropless cataract surgery, developed severe immune-mediated pathologies. The cases reported include primary ocular lymphoma, toxoplasmosis chorioretinitis, and syphilitic retinitis.
Primary Ocular Lymphoma
A 40-year-old woman presented on referral for intraocular inflammation and retinal edema. Medical history included diabetes mellitus and angiomyolipoma. The patient had uneventful dropless cataract surgery in the left and right eyes for blurred vision believed secondary to cataract. Postoperatively, she complained of blurred vision and increased floaters. She was diagnosed with intraocular inflammation and retinal edema and prescribed prednisolone 4 times a day for both eyes but with no effect. On presentation at our institution, corrected distance visual acuity (CDVA) was 20/30 in the right eye and 20/300 in the left eye. Ocular examination was significant for 1+ anterior chamber cell and 1+ vitreous cell. Dilated fundus examination revealed a placoid-like lesion in the left eye and areas of retinal whitening in the macula and areas of retinal vascular sheathing (Figure 1). Differential diagnoses included lymphoma, syphilis, toxoplasmosis, tuberculosis, and sarcoidosis. Laboratory evaluation was negative for syphilis, tuberculosis, sarcoidosis, and toxoplasmosis. Diagnostic pars plana vitrectomy with biopsy of the subretinal lesion was performed on the left eye and confirmed large, B-cell non-Hodgkin’s ocular lymphoma. MRI of the brain and lumbar puncture did not reveal any central nervous system disease. The patient received intravitreal methotrexate injections with resolution of intraocular disease. After 11 months of initial presentation, MRI showed lymphoma activity in the brain. Systemic chemotherapy was started, and the patient is currently inactive.
A 60-year-old man presented on referral for uveitis with decreased vision. Medical history was otherwise unremarkable. He had a history of a scar in his right eye for years and complained of recent worsening of vision. Cataract was suspected, and the patient underwent uneventful dropless cataract surgery in the right eye 1 month prior to presentation. Postoperatively, the patient noted worsening in vision and increased floaters. He was placed on prednisolone every 2 hours for 1 week but failed to improve. At presentation, CDVA was counting fingers in the right eye. Ocular examination showed keratic precipitates and 3+ anterior chamber cell and 2+ vitreous cell. Retinal examination showed arterial thinning and multifocal outer retinal whitening with a patch of whitening adjacent to a chorioretinal scar (Figure 2). Given the clinical presentation and history of old scar, toxoplasmosis chorioretinitis was strongly suspected. A vitreous tap/inject with clindamycin and foscarnet was performed. Results of serum toxoplasmosis titers and vitreous toxoplasmosis polymerase chain reaction were positive. The patient was prescribed double strength sulfamethoxazole/trimethoprim 2 times a day. A second intravitreal injection of clindamycin was delivered 2 weeks later. Improved lesion size was noted 3 weeks after presentation, at which time oral prednisone 60 mg/d was started, and the patient received a third injection of clindamycin. Over the next few months, the patient had an additional recurrence. Nine months after presentation, CDVA was counting fingers, the lesions were inactive, and the patient is on maintenance prophylaxis.
A 49-year-old man presented on referral for retinitis with sudden vision loss, pain, and photophobia. Medical history included syphilis diagnosed 20 years prior to presentation. The patient complained of bilateral decreased vision and underwent uneventful dropless cataract surgery with triamcinolone injection in the right and left eyes, 2 months and 1 month prior to presentation, respectively. Acute vision loss in the right eye began a few weeks postoperatively. The patient was seen by an outside provider, and acute retinal necrosis was suspected. On presentation, CDVA in the right eye was hand motion and, in the left eye, was 20/25. Clinical examination showed 1+ anterior chamber cell and vitritis in the right eye. Anterior chamber of the left eye was quiet. Dilated fundus examination revealed diffuse outer retinal whitening in the right eye and patchy whitening in the left eye (Figure 3). Optical coherence tomography of the right eye showed significant retinal thinning, ellipsoid zone loss, and overall layer disorganization (Figure 3). Fluorescein angiography showed diffuse atrophy and delayed or no perfusion of nasal and temporal areas. Based on the clinical presentation, syphilis was highly suspected. Syphilis immunoglobulin G was positive, and the rapid plasma reagin titer was 1:32. HIV testing was negative. The patient was admitted for a spinal tap, which was VDRL positive, varicella zoster virus immunoglobulin G negative, and contained numerous cells. The patient was started with intravenous penicillin treatment of 4 million units every 4 hours for 2 weeks. Four days after presentation, retinal examination showed improved retinal whitening. Nearly 3 weeks after presentation, CDVA remained hand motion. Repeat optical coherence tomography imaging of the right eye showed outer retinal layer loss. The patient was lost to further follow-up.
Dropless cataract surgery is an attractive option for both providers and patients because the need for strict compliance to eyedrop regimens is removed or at the very least decreased; however, this type of surgery is not without risks. Aside from issues such as compounding errors, antibiotic resistance, and steroid-induced ocular hypertension, immunosuppression is a concern. Overall, complication rates after dropless cataract surgery have remained low and comparable with eyedrop regimens; furthermore, the safety and efficacy of intravitreal steroids have been well established.8–10 But as the use of perioperative injections during cataract surgery has grown so have reports of various complications, including 4 cases of endophthalmitis and 1 case of toxic posterior segment syndrome directly linked to the compounded agent.8,9,11 This is the first report, to our knowledge, of immune-mediated pathologies after dropless cataract surgery with intraocular injection of compounded antibiotics and steroid.
Primary ocular lymphoma is a rare and oftentimes difficult to diagnose malignant cancer. Its nonspecific presentation contributes to ocular lymphoma, being known as a masquerading syndrome; therefore, it is no surprise the patient was initially diagnosed with intraocular inflammation and prescribed prednisolone.12,13 The patient described in this report had received an intravitreal injection of a corticosteroid during her dropless cataract surgery 4 months prior to presentation. The patient's immune status was further dampened by her diabetes mellitus and her prescribed sirolimus, an immunosuppressant. Although a combination of factors most likely played roles in this case of primary ocular lymphoma, caution must be exercised when initiating steroidal agents in patients who already might be immunocompromised.
Just as in the development of the primary intraocular lymphoma, immunosuppression also plays a role in the acquiring of infections. Immunosuppressive drugs and specifically intravitreal injection of triamcinolone have been associated with toxoplasmosis chorioretinitis and other viral etiologies; furthermore, even after apparent immune system recovery, patients might still be susceptible to infection.6,7,14,15 In our series, 2 retinal infectious cases (3 eyes) were further unmasked by the use of intraocular steroids leading to significant retinitis. Their presentation highlights the need for careful preoperative evaluation in patients where long-acting intraocular steroids might be used. The use of intraocular steroids probably led to worsening of their diseases in the short term.
When initiating intravitreal injection of steroidal agents for dropless cataract surgery, providers must be vigilant of their patient’s immune status and evidence of previous retinal infections. As described in the cases of primary ocular lymphoma and syphilitic retinitis, patients who are diabetic, are on immunosuppressant therapies, or have had previous infections might be at increased risk of developing severe immune-mediated pathologies. Furthermore, in the case with toxoplasmosis chorioretinitis, an otherwise healthy individual receiving an intravitreal injection of corticosteroid can still be susceptible to unmasking of a previously dormant infection. The presence of chorioretinal scars, especially multifocal ones, warrant at least a thorough history of previous infectious diseases.
In conclusions, we present, to our knowledge, the first reports of 3 cases of immune-mediated pathologies, 1 of a primary intraocular lymphoma and 2 of infectious retinitis, manifesting after dropless cataract surgery. In each case, compromised immune systems likely contributed to the acquiring of each disease. In cases that use immunosuppressing agents such as intravitreal injection of steroid, close observation should be maintained to ensure the health of the patient and good visual outcomes.
WHAT WAS KNOWN
- Dropless cataract surgery often uses perioperative intraocular injection of steroids.
- Steroids are immunosuppressive agents that create a local environment prone to infection and other pathologies.
WHAT THIS PAPER ADDS
- The first report, to the authors' knowledge, of 3 unique cases of severe immune-mediated pathologies after uneventful dropless cataract surgery.
- When using immunosuppressive agents, patients must be carefully screened for previous immune system compromise prior to initiation and closely monitored afterward to ensure good treatment outcomes.
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