A Prospective Review of Patients Receiving Intravitreal Anti-VEGF: How are we doing during the SARS-Cov-2 Pandemic?

  

    
No.
    
Ethnicity
    
Age
    
Gender
    
LogMAR BCVA
    
Diagnosis
    
Treated eye
    
Systemic Comorbidities
    
Reasons for testing
  
  

    

    

    

    

    
RE
    
LE
    

    

    

    

  
  

    
1
    
W
    
65
    
M
    
0.6
    
0.1
    
Wet AMD
    
R
    
Hypertension
    
Admitted with Chest Pain
  
  

    
2
    
W
    
84
    
M
    
0.3
    
0.4
    
Wet AMD
    
L
    
Pancreatic Ca
    
Pneumonia
  
  

    
3
    
A
    
52
    
M
    
0.1
    
0.3
    
DMO
    
L
    
Kidney Failure
    
Pre-dialysis swab
  
  

    
4
    
W
    
69
    
F
    
0.5
    
0.6
    
Wet AMD
    
R
    
NIDDM
    
District nurse required for home visits
  
  

    
5
    
W
    
84
    
M
    
0.5
    
0.4
    
Wet AMD
    
R
    
Myeloma, Pacemaker
    
Unwell
  

Table 4: Patients tested for SARS-CoV-2 PCR.

Discussion

During the pandemic, the Royal College of Ophthalmologists (RCOphth) produced clinical guidance for the management of ophthalmology services, with the aim of prioritising patients with sight or life threatening conditions and to defer routine appointments and surgeries. With regards to anti-VEGF treatment, patients should continue to receive treatment especially those with wet AMD. Anti- VEGF appointments for patients with DMO and RVO should be deferred unless they have active proliferative retinopathy [7]. The Bright Focus Foundation and American Macular Degeneration Foundation have also advised patients to attend their anti-VEGF appointments as missing injections will lead to poorer visual outcomes [8,9].

As a majority of our patients receiving anti-VEGF therapy are elderly and vulnerable it is vital that measures are put in place to ensure the safety of all of the patients and staff in the eye clinic. It is also important that both clinicians and patients can balance the risk of life-threatening infections such as the SARS-CoV-2 versus the risk of sight threatening condition like wet AMD and, therefore, patients should be triaged accordingly. With regards to Personal Protective Equipment (PPE), the American Academy of Ophthalmology has recommended the use of N95 mask (or a surgical mask if in short supply) and eye protection for the injector, and a surgical mask for the patient due to the close-proximity of the procedure [10,11]. An ophthalmology department in Hong Kong that has gone through the largest outbreak of Severe Acute Respiratory Syndrome (SARS) in the world in 2003 has also recommended the use of eye protection, surgical mask, gown and gloves as a universal precautionary measure during the outbreak [12]. During the course of our study, we have implemented precautions outlined in the ‘introduction’ section to maximise the safety of the delivery of anti-VEGF therapy during the outbreak. As SARS-CoV-2 is shown to have a significant environmental resistance and is able to survive in different biological fluids and secretions, appropriate virucidal disinfection wipes should be used to clean ‘high touch’ surfaces in the department [13,14]. Further, viral RNA is found in conjunctival secretions of patients with SARS-CoV-2 despite having no ocular manifestation [15]. Geller and colleagues recommended the use of povidone-iodine or a combination of chlorhexidine with ethanol and cetrimide against the SARS-CoV [16]. Other alcohol-based solutions like isopropanol or ethanol are also recommended agents. [13,16] During the course of our study, surfaces were cleaned with ‘Sani-Cloth AF Universal Wipes’ (product code: XP00391) by PDI containing Didecyldimethylammonium chloride, which has proven to be effective against the coronavirus [17,18].

We noted that the rate where patients choose to defer their appointment due to the pandemic is higher in the DMO and RVO patient group as compared to the wet AMD group. Only (98/172) 57.0% patients from the DMO and RVO patient group attended anti-VEGF therapy as recommended by clinicians as compared to (239/260) 91.9% patients from the wet AMD group. In total, (22.0%) patients deferred their anti-VEGF appointment. Reasons include patient anxiety and fear, being a nursing home resident as well as the lack of transport due to relatives and friends not being able to bring them into the hospital. Strict lockdown measures were advised by the government to reduce the risk of acquiring infection especially for those with significant comorbidities, resulting in patients deferring their appointments and hospital avoidance. 88 out of 95 patients who deferred their appointments received a telephone call consultation. The remaining seven cancelled and reappointed. Phone consultations include assessment of subjective visual function and latest macular Optical Coherent Tomography (OCT). Wet AMD patients with active disease are advised to attend their appointments to prevent severe visual loss. Patients with stable wet AMD were given option to defer their appointments. Patients willing to attend will be given an appointment accordingly. Others are given the option of further telephone consultations. None of the patients who attended during the study had severe visual deterioration. Nonetheless, patients with high risk of visual loss who did not attend their clinic appointment were given reassurance by the medical retina team of the precautions in place.

Patients in the DMO group have significantly higher proportion of minority ethnic population as compared to the two other groups (Table 3) [P<0.001]. Both these risk factors are associated with higher morbidity and mortality rates from SARS-CoV-2 [4]. As a result, more patients with DMO defer or cancelled their appointments to reduce their risk of acquiring the infection. As for wet AMD patients, we observed that the majority of the patients are still attending their clinic appointments despite the ongoing pandemic. Patients with wet AMD are also in the more vulnerable age group (78.84±9.76) as compared to RVO (67.63±13.26) and DMO (59.28±14.54). About one-third (33.9%) of wet AMD patients received injections in their ‘better eye’ as compared to RVO (15.0%) and DMO (13.8%) [P<0.001]. More patients from the AMD group have VA of worse than 1.0 LogMAR in their better eye (P=0.44). Subjectively, more patients from the wet AMD group reported ‘recent deterioration of vision’ as compared to the RVO and DMO group (40.2% vs. 37.5% vs. 22.4%) [P=0.04]. This is likely due to the fear and anxiety of visual loss especially during the course of the pandemic.

In East Lancashire Hospital NHS Trust, we serve an estimated population of 461,866. Approximately 376,182 (81.5%) of the population are Caucasian, 77,615 (16.8%) are Asian (Pakistani, Indian, Bangladeshi, Chinese) and 8,069 (1.7%) others [19]. As Caucasians have the highest risk and a genetic predisposition of developing AMD followed by Chinese and Hispanics, we can see a higher number of Caucasian in the wet AMD group (98.7%) as compared to Asians (1.3%) [P<0.001] [20]. On the other hand, the DRIVE UK study has shown that minority ethnic communities with non-insulin dependent diabetes are more likely to develop diabetic retinopathy and sight threatening maculopathy as compared to Caucasians [21]. Almost 1 in 5 who attended during the course of study in the DMO group is minority ethnic (19.0% vs. 81.0%) as compared to patients in the RVO (7.5% vs. 92.5%) and AMD group (1.3% vs. 98.7%) [P<0.001]. Although patients are younger in the DMO group as compared to the wet AMD group, they have more systemic comorbidities making both vulnerable groups of patients.

As symptomatology of SARS-CoV-2 are vague and common, we had patients that attended the eye clinic with symptoms such as longstanding cough or shortness of breath. As smoking is a risk factor for wet AMD, there was a fair amount of patients with COPD in the wet AMD group as compared to other groups (14.2% vs. 5.0% vs. 3.4%) [P=0.03]. It is vital that these patients are aware that they should not be excluded from receiving treatment provided that their symptoms are not new. We communicated this information through leaflets and telephone calls. It is also difficult to pinpoint asymptomatic carriers of the infection and super spreaders of the infection hence universal precaution is necessary to maximise the safety of our vulnerable patients whilst receiving treatment.

Due to the crisis, temporary coding and managerial systems have been put in place to ensure that all patients receive a telephone consultation should they choose to defer their appointments due to the pandemic. An ongoing study is being carried out to assess the visual outcomes as a result of delay in anti-VEGF treatment, to further contribute to available data. Surgical facemasks, similar to other clinical wastes can act as fomites spreading infection if not used appropriately. To combat this, we ensure that all patients attending the eye clinic are given clear instructions on the use of facemasks whilst in the department and a safe disposal of facemask on exit. Furthermore, the use of facemasks in all departments can lead to national supply shortages and hence the applicability of this practice can be argued. Nonetheless, our measures have proven to be safe with no infectivity within the department during the period of study, especially when a safe distance cannot be maintained between two people during an intravitreal injection.

Conclusion

None of the patients in our study contracted SARS-CoV-2 during the lock down period. Our study has shown the safety of anti-VEGF therapy with the current precautionary measures despite caring for a vulnerable group of patients. Therefore, patients should be reassured to attend injection appointments to prevent further visual loss and to maintain independence.

What was known before

• SARS-CoV-2 is highly infectious.

• Missing or delaying anti-VEGF is associated with poorer visual outcomes.

• Minority ethnic population in the UK is at a higher risk of SARS-CoV-2 and their associated complications.

What this study adds

• There is no incidence of SARS-CoV-2 as a result of the current precautionary measures in the eye department.

• Majority of wet AMD patients are still attending anti- VEGF appointments notwithstanding the pandemic.

• DMO and RVO groups comprise of higher proportion of minority ethnic patients and hence these groups of patients were more cautious in attending the hospital for their appointment.

• Telephone consultation, may be adopted as another option to help with the increasing capacity of the medical retina service alongside with virtual clinics.

References

1. Thng ZX, Smet MD, Lee CS, Gupta V, Smith JR, McCluskey PJ, et al. COVID-19 and immunosuppression: a review of current clinical experiences and implications for ophthalmology patients taking immunosuppressive drugs. British Journal of Ophthalmology. 2020.
2. Yu AY, Tu RX, Shao X, Pan AP, Zhou KJ, Huang JH. A comprehensive Chinese experience against SARS-CoV-2 in ophthalmology. Eye and Vision. 2020; 7.
3. Kucharski AJ, Klepac P, Conlan AJ, Kissler SM, Tang ML, Fry H, et al. Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study. The Lancet. 2020; 20: 1151-1160.
4. Joseph T, Ashkan M. International Pulmonologist’s Consensus on COVID-19. 2020.
5. Public Health England. Beyond the data: the impact of COVID-19 on BAME groups. 2020.
6. Syrek R. COVID-19 Daily: High-Risk Specialties, Flu Comparisons. 2020.
7. The Royal College of Ophthalmologists. Medical Retinal Management Plans during COVID-19. 2020.
8. Bright Focus Foundation. Macular Degeneration & Coronavirus: Tips for Patients. 2020.
9. American Macular Degeneration Foundation. Coronavirus and Your Macular Degeneration Care. 2020.
10. American Academy of Ophthalmology. Alert: important coronavirus updates for ophthalmologists. 2020.
11. Safadi K, Kruger JM, Chowers I. Ophthalmology practice during the COVID-19 pandemic. BMJ Open Ophthalmology. 2020; 5: e000487.
12. Chan WM, Liu DTL, Chan PKS, Chong KKL, Yuen KSC, Chiu TYH, et al. Precautions in ophthalmic practice in a hospital with a major acute SARS outbreak: an experience from Hong Kong. Eye. 2005; 20 283-289.
13. Geller C, Varbanov M, Duval RE. Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies. Viruses. 2012; 4: 3044-3068.
14. European Centre for Disease Prevention and Control. Disinfection of environments in healthcare and non-healthcare settings potentially contaminated with SARS-CoV-2. 2020.
15. Karimi S, Arabi A, Shahraki T, Safi S. Detection of severe acute respiratory syndrome Coronavirus-2 in the tears of patients with Coronavirus disease 2019. Eye. 2020; 34: 1220-1223.
16. Lim LW, Yip LW, Tay HW, Ang XL, Lee LK, Chin CF, et al. Sustainable practice of ophthalmology during COVID-19: challenges and solutions. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2020; 258: 1427-1436.
17. PDI. Sani-Cloth AF Universal. 2020.
18. ECRI. Disinfectant concentrations and contact times for EPA’s list of products effective against novel coronavirus SARS-CoV-2, the cause of COVID-19. Health Devices. 2020.
19. Lancashire GOV. Lancashire’s population by ethnicity, 2011 Census of Population. 2020.
20. WebMD. How does race and ethnicity affect your risk for Age-Related Macular Degeneration (AMD)?. 2020.
21. Sivaprasad S, Gupta B, Gulliford MC, Dodhia H, Mohamed M, Nagi D, et al. Ethnic Variations in the Prevalence of Diabetic Retinopathy in People with Diabetes Attending Screening in the United Kingdom (DRIVE UK). Plos One. 2012; 7: e32182.