Lynda Charters

home

authors

lynda-charters

Endophthalmitis is a rare occurrence in ocular surgery but the percentage, no matter how small, remains unacceptable. Dr Winfried M. K. Amoaku, associate professor/reader in ophthalmology and Hon consultant ophthalmologist, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom, recently described the management protocol followed in the UK to treat older patients with endogenous endophthalmitis.

The endogenous form of the infection is exceedingly rare, occurs in 1 per 1 million cases annually and accounts for about 10% of all endophthalmitis. Intraocular infection occurs as the result of haematogenous spread from a distant non-ophthalmic source and may be bacterial, fungal, parasitic or viral.

Dr Amoaku explained that the patients most (but not exclusively) likely to develop endogenous endophthalmitis are immunocompromised, and include those with diabetes, systemic cancer and HIV, as well as those taking antineoplastic therapies, broad-spectrum antibiotics and immunomodulatory agents. The presentation of the infection includes varying degrees of pain, inflammation and visual loss.

Eliminating the potential land mines in glaucoma surgery

The clinical examination shows the presence of an anterior segment inflammation, vitreous opacification, choroidoretinal infiltrates, retinal haemorrhages, cotton-wool spots and retinal vasculitis. The progression of the infection depends on the causative organism. With a bacterial infection, rapid progression is expected, fungal infections progress slowly and the speed of viral progression can vary.

Dr Amoaku warned about the “fair degree” of misdiagnosis, which is as high as about 63%. “A high degree of suspicion for endophthalmitis is needed to establish the diagnosis,” he cautioned. He also noted the importance of ruling out intraocular lymphoma, which mimics endogenous endophthalmitis.

Dr Amoaku cited a 2018 report of the British Ophthalmological Surveillance Unit

 that included 48 patients (median age 56.9 years) from December 2013 to December 2014. About 46% of patients were older than 60, the oldest being 85.

Considering the best surgical approach in angle closure patients

The presenting features in these patients included cellulitis; afferent pupillary defect; corneal clarity; anterior chamber cells; hypopyon; fibrin; vitritis; retinitis; and others, which were similar to those reported in the literature. “Typically, in these patients the endophthalmitis was unilateral and included bacterial, viral and fungal infections,” he said.

Upon presentation, the vision was already poor, with a median of 3 logarithms of the minimum angle of resolution visual acuity (logMAR VA). Several infection sources identified in addition to the strong association with diabetes included septic arthritis, colon cancer, cardiac valve disease and intravenous drug use.

Considering antibiotics use in postoperative endophthalmitis

The blood cultures were positive in 58% of patients; in contrast, vitreous biopsies were positive in only about 23%. The causative organism was more likely to be identified in patients who presented early after the onset of symptoms. Treatment included a combination of systemic intravenous or oral antibiotics, intravitreal antibiotics, antifungal drugs and mostly topical corticosteroids.

A total of 25 patients, including one who died, were followed for 6 months. The median visual acuity (VA) was 0.18 logMAR; the VA was below one in four of 23 patients and below 0.3 in 19 patients. Poor outcomes were characterised by no light perception and light perception VA.

UK treatment recommendations: systemic and ocular

“A full systemic work-up is necessary to determine the source of the infection and a high degree of suspicion is required,” Dr Amoaku said. “The mandatory examinations include ophthalmic ultrasound and intraocular biopsy of the vitreous for microscopy, culturing and sensitivity and blood cultures. Cardiac echography, abdominal ultrasound and MRI are indicated as appropriate.” Importantly, Dr Amoaku noted that diabetes must be excluded in all cases.

The intraocular treatment begins based on the clinical features and presumed diagnosis. After the vitreous biopsy results are received, treatment is modified as needed. Intravitreal therapy includes vancomycin 1 mg/0.1 ml plus amikacin 0.4 mg/0.1 ml or ceftazidime 1 mg/0.1 ml for bacterial infections and amphotericin B for fungal infections. Ganciclovir is prescribed for viral infections.

Study: Identifying link between endophthalmitis, coronavirus

At 3–5 days after the initial treatment, the treatment is repeated depending on the diagnosis and the response. Vitrectomy is reserved to treat a few selected cases.

Dr Amoaku emphasised that the systemic anti-infective treatment specific to the infectious agent is mandatory for all cases. When the infection is under control, systemic corticosteroids can be started.

Maling S, King C, Davies N. A British Ophthalmological Surveillance Unit study on metastatic endogenous endophthalmitis. Eye (Lond). 2018;32:743-748.

This article is adapted from Dr Amoaku’s presentation at the American Academy of Ophthalmology’s 2020 virtual annual meeting. Dr Amoaku has no financial interest in this subject matter.

Articles

In endophthalmitis, the systemic anti-infective treatment specific to the infectious agent should always be used. 

Addressing endogenous endophthalmitis in patients

Periodic aflibercept (Eylea; Regeneron Pharmaceuticals) treatment for moderate to severe nonproliferative diabetic retinopathy (NPDR) resulted in fewer patients developing PDR or centre-involving diabetic macular oedema (DMO), although no positive effect on visual acuity (VA) was seen, according to Raj K. Maturi, MD, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, who reported the interim 2-year results of the DRCR Retina Network Protocol W study.

“Eyes with moderate to severe NPDR are at high risk for disease progression and development of vision-threatening complications,” Maturi stated, underscoring the importance of determining whether aflibercept prevents development of PDR and centre-involved DMO as well as the potential for a visual benefit at the later 4-year point.

Protocol W is a randomised multicentre clinical trial of adults with type 1 or 2 diabetes and severe NPDR in at least 1 eye. Included patients had no evidence of neovascularisation on fluorescein angiography and a best-corrected VA letter score of 79 or higher, ie Snellen acuity of 20/25 or better. Patients were randomly assigned to receive either 2 mg of periodically administered intravitreous aflibercept or sham injection. Monthly injections were administered for the first 3 visits and followed by injections at months 4, 8 and 12. Before 2 years, injections were administered at each visit, with subsequent treatment with aflibercept only if the diabetic retinopathy exceeded mild NPDR.

Evaluating patients for a retinal disorder (video)

The primary outcome was the cumulative probability of development of PDR or centre-involving DMO with vision loss. Treatment was deferred if the eye had no worse than mild NPDR. Aflibercept was administered in both groups if centre-involving DMO with vision loss or high-risk PDR developed.

A total of 399 eyes of 328 patients were included (mean age, 56 years), all of whom had moderate to severe NPDR. Of these, 200 were randomised to aflibercept and 199 to sham treatment; data from all these patients were included in the primary analysis.

At 2 years, more patients randomised to sham therapy developed DMO or PDR compared with those randomised to aflibercept (44% vs 16%, respectively; adjusted HR, 0.32; P < .001), Maturi reported.

The time to development of PDR was 33% in the sham group and 14% in the aflibercept group. The time to development of DMO was 15% in the sham group and 4% in the aflibercept group. “The criteria for the development of the first PDR and/or DMO [were] met in 35 patients in the aflibercept group and 81 patients in the sham group,” Maturi said.

DMO study shows robust efficacy of intravitreal dexamethasone implant

Most patients in both groups developed neovascularisation of the disc and/or neovascularisation elsewhere, 4 patients in each group developed vitreous haemorrhage and 1 patient in the sham group developed neovascularisation of the iris compared with no patients in the aflibercept group.

VEGF therapy was administered to 3 patients in each group, and focal or grid laser for DMO was administered in 1 patient in the sham group.

Analysis conducted to determine a correlation between the baseline NPDR severity and development of DMO or PDR indicated a definite relationship based on more severe disease.

“Among patients with the lowest levels of NPDR, only 3% in the aflibercept group went on to develop DMO or PDR compared with 24% in the sham group,” Maturi said. “Among patients with severe NPDR, 36% went on to develop DMO or PDR in the aflibercept group, and 68% did so in the sham group despite regular treatments.”

Analysis of the change in the severity of diabetic retinopathy at 2 years showed that 5% of patients in the aflibercept group had a 2-step worsening of disease compared with 12% in the sham group. Regarding improvement, 45% of patients in the aflibercept group had a 2-step or greater improvement compared with 14% in the sham group.

Diabetes and DR: Making progress in the global epidemic

Comparison of the 2 treatment groups showed almost no difference in adjusted mean VA over 2 years. The central subfield thickness improved slightly and nonsignificantly by –6 microns in the aflibercept group and –1 micron in the sham group.

About 5 injections of aflibercept were administered for DMO and 0.3 in the sham group; over 2 years, the aflibercept patients received 8 injections and the sham-treated patients received 1.1 injections.

Adverse events associated with aflibercept included 3 cases of endophthalmitis, 2 of retinal detachment, 13 of IOP spikes of 10 mm Hg or higher and 8 of IOP elevations of 30 mm Hg or higher. In the sham group, 2 patients had retinal detachments, 12 had IOP spikes of 10 mm Hg or higher and 3 had IOP spikes of 30 mm Hg or higher.

Common types of retinal disorders explored (video)

Hypertension was the systemic event seen in more patients, with 18 in the aflibercept cohort and 13 in the sham group.

The major study findings indicated that among eyes with moderate to severe NPDR, the proportion that developed PDR or centre-involving DMO was lower with periodic aflibercept treatments compared with sham treatment through the 2-year point. Preventive treatment with aflibercept did not confer a VA benefit compared with anti-VEGF initiated after PDR or DMO development.

Maturi pointed out that this 4-year study may be important to determine whether preventing PDR and centre-involved DMO improves the long-term outcomes.

This article was adapted from Maturi’s presentation at the Association for Research in Vision and Ophthalmology 2021 virtual annual meeting. He has no financial interest in this subject matter.

The proportion of eyes that developed PDR or centre-involving DMO was lower with periodic aflibercept treatments compared with sham treatment through the 2-year point.

Study evaluates periodic aflibercept injections in NPDR treatment

 without eyedrops has long been a goal for ophthalmologists. However, whilst it may be possible one day, it is not yet a reality and anti-glaucoma drops currently remain the first-line choice for many ophthalmologists.

Numerous surgical procedures and minimally invasive devices are also available to lower intraocular pressure (IOP). Some have been around for a long time, but within the past few years, numerous devices have entered the market with unknown long-term results and there are more still in the pipeline.

Despite great progress in the field, the question remains as to which glaucoma treatment(s) can achieve and maintain the desired IOP level and prevent progression, according to Dr Janet B. Serle, professor emeritus of ophthalmology, Icahn School of Medicine at Mount Sinai, New York, United States.

Clinicians can adhere to the general guidelines that have been established for target IOPs for different glaucoma stages, however, how well they work for individual patients remains to be seen. “For each patient, it is important to assess the risk parameters in addition to the stage of the disease,” Dr Serle said. “In some patients, we can hopefully get ahead of progression by treating the glaucoma aggressively, and in other patients we may be able to step back, accept higher target IOPs and carefully assess the most appropriate therapies.”

Many large clinical trials have evaluated specific procedures over different follow-up periods of time. The trials have generated widely varying outcomes regarding medication use and wide-ranging IOP results postoperatively. These range from no medications needed in 78% of patients followed for 3 years after selective laser trabeculoplasty (SLT)

 to studies of minimally invasive glaucoma surgeries (MIGS) and gonioscopy-assisted transluminal trabeculotomy that resulted in a wide range of medications needed postoperatively.

Dr Serle suggested that surgeons look outside the treatment box, rethink the current order by which they select treatment and determine if they should adjust that order. For example, should surgeons consider an SLT, an earlier SLT or a MIGS procedure, if appropriate, or should patients be treated more aggressively earlier in the disease process, especially in the case of young patients with potentially longer life spans? Another challenge, she pointed out, is identifying and diagnosing patients with early disease.

“I do not think it is time to abandon the traditional more invasive procedures, particularly in advanced disease, because these more consistently result in lower IOPs,” she commented.

Currently, however, although there are numerous non-medical options that are available for glaucoma management, physicians cannot now achieve successful IOP control in all patients without relying on medical therapy.

Using pivotal study data to guide glaucoma patient management decisions

Dr Serle emphasised that to manage and control glaucoma without eyedrops, there must be a more “robust” way to identify patients with glaucoma, especially those with early disease. Acceptance and incorporation of other, newer treatment options by patients and physicians should occur.

If intervention is successful, the progression curve may change, she said, and she noted the importance of demonstrating that surgical devices and procedures achieve satisfactory target IOPs for long durations during a patient’s life. The current devices meet the target IOPs in some patients, but the long-term results are unknown.

Dr Serle said that it should be a goal to reduce the medication burden as much as possible. “Physicians can think about how they select treatment,” she said. “For patients with early-stage glaucoma, consider options other than medications.”

Precision management to revolutionise glaucoma diagnosis and treatment

She added: “In moderate and late-stage disease, treatment with laser and/or MIGS and/or traditional surgery may reduce or eliminate the need for medications in some patients. For late-stage disease, more invasive surgeries may be more successful at achieving the required IOP with fewer or no medications.”

Gazzard G, Konstantakopoulou E, Garway-Heath D, et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. 

This article is adapted from Dr Serle’s presentation at the American Glaucoma Society’s 2021 virtual annual meeting. Dr Serle is a consultant to Aerie Pharmaceuticals, Allergan, Bausch + Lomb and Qlaris.

Ophthalmologists should consider numerous options for treating individual glaucoma patients, including non-medical interventions.

Dropless glaucoma treatment: An elusive path to ease burden

Horner’s syndrome is characterised by ipsilateral ptosis, miosis and anhidrosis that result from a lesion affecting the oculosympathetic pathway. The syndrome can be benign if idiopathic or iatrogenic, however, it can also be predictive of a life-threatening event such as demyelinating inflammatory, infectious, vascular or neoplastic problems.

It is important to promptly and accurately diagnose the cause; ophthalmologists are likely to be on the front lines. According to Dr Aaron M. Fairbanks, a senior ophthalmology resident at Mayo Clinic, Rochester, Minnesota, United States, no definitive information is available about the pathologies associated with Horner’s syndrome and the incidence rate in US adults is unknown.

Because no US population-based studies of the syndrome had been undertaken, Dr Fairbanks and his colleagues set out to determine its population-based incidence in adults, evaluate the underlying causes and disease manifestations, and investigate the value of imaging in patients with a neurologically isolated Horner’s syndrome.

Uveitis: A leading and underestimated cause of visual morbidity in patients

The investigators conducted a retrospective chart review of all adults diagnosed with Horner’s syndrome in Olmsted County, Minnesota, using the Rochester Epidemiology Project database, between 1 January 2000 and 31 December 2018. According to Dr Fairbanks, the team of investigators reviewed the charts for the correct diagnoses, and recorded the patient demographic data, presenting signs and symptoms, imaging results and aetiologies, and analysed all the results.

Of the 736 patients identified in the review of cases, 78 confirmed cases were included in the study; the rest were excluded because of their non-resident status, disease onset outside the study time frame, or miscoded or incorrect diagnoses.

According to the team of investigators, the causes varied widely from those that were benign, including idiopathic and surgical causes, cluster headache and goitre, to neurologically or systemically dangerous causes including carotid artery dissection; stroke; neoplastic and traumatic causes; varicella zoster; arteriovenous fistula; and fibromuscular dysplasia.

The median patient age was 57 years and all patients were white. The age- and sex-adjusted incidence of Horner’s syndrome during the study period was 4.24/100,000/year with no difference in sex or over time.

“We did find a significant [P < 0.001] difference across age groups, with older patients having a higher incidence of Horner’s syndrome,” Dr Fairbanks pointed out. Three-quarters of cases were diagnosed by neurologists and ophthalmologists, with most diagnosed clinically. “Interestingly,” Dr Fairbanks said, “idiopathic cases were more likely to be confirmed with cocaine or apraclonidine eyedrop testing (P = 0.002), and stroke, surgical and dangerous causes were more often diagnosed clinically (P = 0.008).”

The most common aetiologies were idiopathic (20 patients, 25.6%), followed by internal carotidartery (ICA) dissection (15 patients, 19.2%), stroke (12 patients, 15.4%), surgical (12 patients, 15.4%) and neoplastic (11.5%). Analysis of the aetiologies indicated that about 56% of cases had a dangerous neurological or systemic origin, according to investigators.

Compared with other aetiologies, the patients with ICA dissections—which were more likely to be diagnosed in younger individuals with a mean age of 49 years (P = 0.02)—were more likely to have pain (P < 0.001), facial paraesthesia (P = 0.007), blurred vision (P = 0.04) and photophobia (P < 0.004). Most of the cases with a stroke had a lateral medullary infarction.

Targeting neurodegenerative diseases using risuteganib

Neoplastic causes included four Pancoast tumours that affected the oculosympathetic pathway at the lung apex. It was noted that the most common neoplasm was lung cancer.

Moreover, as Dr Fairbanks explained, the investigators found that neuroimaging results were surprising in that almost 40% of patients with a neurologically isolated Horner’s syndrome had a positive finding on computed tomography (CT) or magnetic resonance imaging (MRI). Dr Fairbanks went on to note that in isolated Horner’s syndrome cases, pain suggested both a dangerous aetiology and a positive imaging result, which was driven primarily by patients found to have an ICA dissection.

In this first US population-based study of the incidence of Horner’s syndrome, the primary take-home point is that 56.4% of cases resulted from a dangerous cause; in previous reports the percentages ranged from 8% to 78%. Another finding useful in diagnosis is that about 40% of patients with an isolated Horner’s syndrome had positive CT or MRI findings, which is almost double the percentage reported previously.

Discerning among clinical aetiologies of paediatric conjunctival tumours

Finally, investigators noted that pain reported by patients suggested a dangerous aetiology and positive imaging, which in this study was most likely to be secondary to an ICA dissection. Ophthalmologists should keep in mind that ICA dissections are likely to occur in younger patients, may look like an isolated syndrome or present with neurological disease and stroke, are painful, and may cause facial paraesthesia, blurred vision or photophobia, compared with other causes.

“We recommend imaging of the oculosympathetic pathway in all cases of Horner’s syndrome without a clear aetiology, even in neurologically isolated cases, particularly when pain is present,” Dr Fairbanks emphasised.

This article is adapted from Dr Fairbanks’ presentation at the American Academy of Ophthalmology’s virtual annual meeting. Dr Fairbanks has no financial interest in this subject matter.

Investigators found that 56.4% of Horner’s syndrome cases resulted from a dangerous cause. 

Author | Lynda Charters

Articles

Study evaluates periodic aflibercept injections in NPDR treatment

Dropless glaucoma treatment: An elusive path to ease burden

Shedding light on Horner’s syndrome

Addressing endogenous endophthalmitis in patients