Bradley and Delaffon conducted a literature review regarding diabetic retinopathy screening (DRS) in people with severe mental illness (SMI) (1). People with SMI have reduced attendance at DRS, because of poorer compliance with general diabetic care. The authors verified that anxiety and depression were barriers in attending DRS and strategies of preventative health programs such as DRS should be developed and prepared for people with SMI. I want to present two information.
Chen and Lu reviewed the association between diabetic retinopathy (DR) and depression (2). Depression in patients with DR had a negative effect on the condition of DR, and they recommended psychiatric therapies for depression to achieve optimal prognosis in patients with DR and depression. Diabetes control is closely related to keeping good lifestyles including nutrition, exercise, resting and stress management. Taken together, diabetes supporting system in patients with depression could be developed by comprehensive medical and health care strategies.
Khoo et al. specified that severity of DR, diabetic macular edema (DME) and vision loss were significantly associated with poor psychosocial outcomes (3). Bi-directional associations might be existed and increased incidence and progression of DR was predominant in subjects with depression or depressive symptoms. Based on a systematic review, they proposed two actions. First, prevention of poor psychological outcomes is needed by delaying pro...
Khoo et al. specified that severity of DR, diabetic macular edema (DME) and vision loss were significantly associated with poor psychosocial outcomes (3). Bi-directional associations might be existed and increased incidence and progression of DR was predominant in subjects with depression or depressive symptoms. Based on a systematic review, they proposed two actions. First, prevention of poor psychological outcomes is needed by delaying progression of DR/DME. Second, early detection and management of poor psychological functioning is needed by improving screening tools and medical/health care systems for patients. Diabetes and its complication management have some difficulties even in patients without SMI. As there is a limitation in personal effort, improvement of accessibility to medical/health care system is needed in patients with SMI.
1. Bradley ER, Delaffon V. Diabetic retinopathy screening in persons with mental illness: a literature review. BMJ Open Ophthalmol 2020;5(1):e000437.
2. Chen X, Lu L. Depression in Diabetic Retinopathy: A Review and Recommendation for Psychiatric Management. Psychosomatics 2016;57(5):465-471. doi:10.1016/j.psym.2016.04.003
3. Khoo K, Man REK, Rees G, Gupta P, Lamoureux EL, Fenwick EK. The relationship between diabetic retinopathy and psychosocial functioning: a systematic review. Qual Life Res 2019;28(8):2017-2039. doi:10.1007/s11136-019-02165-1
Thank-you to the authors for sharing their departmental protocol based current international research and recommendations . We have put in place many of the precautions outlined however wished to share our recent experience with regard to intravitreal injections (IVI), and additional measures put in place as a result.
IVIs have continued in our service for sight threatening pathology throughout the UK government lockdown of the past 8 weeks. Patients have self-isolated for 7 days prior to their procedure and are screened for symptoms of COVID19 or contacts before attendance. Arriving at our facility they wash their hands, don a surgical mask and have their temperature, oxygen saturations and blood pressure checked. Social distancing is maintained in waiting areas by blocking alternate seats as mentioned.
For the procedure itself the patient is draped and injectors wear sterile gloves, a theatre gown and a fluid resistant surgical mask as per national guidance .
There was no protocol to routinely test patients attending for IVI at our units for coronavirus, however tests were performed on four consecutive injection lists on 4th and 5th May. 48 patients were tested with a mean age of 76 years (range 54-92). 2 (4%) tested positive despite being asymptomatic. They were asked not to attend and will be rescheduled. 4 (13%) decided not to attend voluntarily.
As mentioned by the authors retinal services tend to serve an elderly population with a...
As mentioned by the authors retinal services tend to serve an elderly population with a high prevalence of co-morbidities. This puts them at high risk of significant morbidity and mortality from COVID-19. Although a small opportunistic sample our observations suggest that simply isolating and screening symptomatic patients cannot guarantee a list free from the risk of potential transmission amongst this at risk population.
As a result of the above and in addition to the measures outlined we feel we should now swab test all patients 3 days prior to their attendance.
Furthermore, given the close contact inherent in performing injections and in line with recommendations from our Hong Kong colleagues based on experience from the SARS outbreak  we feel that IVIs should be considered high risk procedure for transmission and staff supported in wearing personal protective equipment that makes them feel safe. This is generally felt to be a filtering face piece (FFP3) mask and a protective visor in addition to a surgical gown and gloves.
We look forward to hearing from colleagues elsewhere as to how they approach this issue.
 Safadi K, Kruger J, Chowers I, Solomon A, Amer R, Aweidah H et al. Ophthalmology practice during the COVID-19 pandemic. BMJ Open Ophthalmology. 2020;5(1):e000487.
 Public Health England. Recommended PPE for healthcare workers by secondary care inpatient clinical setting, NHS and independent sector. 2020 p. 33.
 Chan W, Liu D, Chan P, Chong K, Yuen K, Chiu T et al. Precautions in ophthalmic practice in a hospital with a major acute SARS outbreak: an experience from Hong Kong. Eye. 2005;20(3):283-289.
Table 1. Complement Levels for Cases with Intermediate AMD Versus Controls.
(n = 109)
(n = 65)
(95% CI) †
77 (68 – 90)
90 (82 – 96)
0.96 (0.94 – 0.98)
107 (98 - 118)
113 (99 – 127)
0.99 (0.97 – 1.00)
4.5 (3.5 – 5.5)
3.5 (2.5 – 4.6)
1.29 (1.07 – 1.59)
784 (295 – 1,269)
522 (296 – 1,239)
1.00* (1.00 – 1.01)
10 (9 – 12)
11 (9 – 12)
0.91 (0.79 – 1.03)
78 (66 – 92)
70 (53 – 81)
1.01 (1.00 – 1.02)
Factor B (µg/mL)
111 (100 – 127)
125 (108 – 137)
0.98 (0.96 – 0.99)
Factor D (µg/mL)
1.7 (1.4 – 2.2)
1.8 (1.5 – 2.1)
1.04 (0.86 – 1.32)
19 (18 – 23)
19 (16 – 22)
1.11 (1.01– 1.24)
61 (50 - 76)
50 (41 – 62)
1.03 (1.01 – 1.05)
654 (561 - 834)
882 (657 - 1119)
0.97* (0.95 – 0.98)
722 (617 - 876)
597 (522 - 709)
1.03* (1.01 – 1.05)
Factor H (µg/mL)
198 (177 – 226)
221 (195 – 251)
0.99 (0.98 – 0.99)
Factor I (µg/mL)
26 (22 – 29)
31 (28 – 34)
0.83 (0.77 – 0.89)
39 (34 – 44)
45 (40 – 49)
0.94 (0.90 – 0.98)
703 (575 – 793)
564 (448 – 692)
1.04* (1.02 – 1.07)
181 (158 - 213)
164 (144 – 197)
1.06*(0.99 – 1.15)
* OR corresponding to change in 10 units of complement factor
†OR = Odds ratio from the multivariable logistic regression with 95% Confidence Intervals (CI) after adjusting for age and family history of AMD.
‡ P-values obtained from multivariate logistic regression including age and family history of AMD and adjusted for multiple comparisons using FDR
§ P-values obtained from multivariate logistic regression including age and family history of AMD and adjusted for multiple comparisons using the Bonferroni statistical correction
We read with interest the role of complement in age-related macular degeneration (AMD) explored by Lynch and colleagues1. The authors have expertly examined the numerous components of the complement system and provided much novel data, particularly in the context of intermediate AMD.
Their results are congruent with that of the literature, especially with regard to lower levels of C3a, C5a and Ba in the setting of AMD2. Furthermore, the results of the FILLY trial have shown positive effects of the inhibition of C3 in limiting geographic atrophy and thus lend an element of support to the conclusions of this study3. We hope that the subsequent phase 3 trials – DERBY and OAKS – will lend further support and allow research such as this to translate to clinical benefit for patients4.
However, we do feel that there may be an element of multiple hypothesis testing evident in this study that increases the risk of generating some erroneous results. We feel a Bonferroni statistical correction would have been an appropriate tool to add further robustness to the positive findings that have been demonstrated. We especially feel that the results relating to the inhibitory factors of the complement system do not tend to correlate with some of the findings in the literature. Although Lynch et al have identified lower levels of Factor B, Factor H and Factor I in the AMD arm of the study, there are numerous reports in the literature reporting the opposite...
However, we do feel that there may be an element of multiple hypothesis testing evident in this study that increases the risk of generating some erroneous results. We feel a Bonferroni statistical correction would have been an appropriate tool to add further robustness to the positive findings that have been demonstrated. We especially feel that the results relating to the inhibitory factors of the complement system do not tend to correlate with some of the findings in the literature. Although Lynch et al have identified lower levels of Factor B, Factor H and Factor I in the AMD arm of the study, there are numerous reports in the literature reporting the opposite results where levels of these factors are higher in AMD patient populations, albeit not in settings with identical severity of disease2,5,6.Whether the results presented in this study constitute a true finding in the setting of intermediate AMD or whether this represents a statistical type 1 error, it would be difficult to ascertain.
Overall, this study shines more light on this intricate topic with clinically significant results. We hope this will stimulate further research and discussion in the field.
1. Lynch AM, Palestine AG, Wagner BD, et al. Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging. BMJ Open Ophthalmol 2020;5:e000361. doi:10.1136/bmjophth-2019-000361
2. Scholl HPN, Issa PC, Walier M, et al. Systemic Complement Activation in Age-Related Macular Degeneration. Toland AE, ed. PLoS One 2008;3:e2593. doi:10.1371/journal.pone.0002593
3. Apellis Pharmaceuticals. Apellis Pharmaceuticals Announces That APL-2 Met Its Primary Endpoint in a Phase 2 Study in Patients with Geographic Atrophy, an Advanced Form of Age-Related Macular Degeneration Statistically Significant Slowing of Disease Progression Seen at 12 Months. 2017. Accessed January 26, 2020.
4. Apellis Pharmaceuticals. Recruiting patients with geographic atrophy secondary to AMD for phase 3 trials | Apellis APL-2 Opthalmic Trial. . Accessed January 26, 2020.
5. Hecker LA, Edwards AO, Ryu E, et al. Genetic control of the alternative pathway of complement in humans and age-related macular degeneration. Hum Mol Genet 2010;19:209-215. doi:10.1093/hmg/ddp472
6. Silva AS, Teixeira AG, Bavia L, et al. Plasma levels of complement proteins from the alternative pathway in patients with age-related macular degeneration are independent of Complement Factor H Tyr402His polymorphism. Mol Vis 2012;18:2288-2299.