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Aims: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits. Methods: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO). Results: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively). Conclusion: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women.

Aims: To evaluate the prevalence and severity of diabetic retinopathy including macular oedema in pregnant women with diabetes and to identify women in whom the frequency of retinal screening can be reduced to minimize the burden of health care visits. Methods: A cohort study of 348 women with pre-existing diabetes were routinely screened with retinal photo in early (12 weeks) and late pregnancy (27 weeks). Diabetic retinopathy was classified in five stages in accordance with National Danish Guidelines based on the eye with the highest retinopathy level. Sight-threatening retinopathy was defined as the presence of proliferative retinopathy and/or clinically significant macular oedema (CSMO). Results: Retinopathy was present in 52% (116/223) vs. 14% (17/125), with sight-threatening retinopathy in 16% (35/223) vs. 6% (7/125) of women with type 1 and type 2, respectively. Women without retinopathy in early and late pregnancy were characterized by shorter diabetes duration (p < 0.0001 and p = 0.008) and predominance of type 2 diabetes. Amongst the 50% (175/348) of the cohort having no retinopathy in early pregnancy and HbA1c<53 mmol/mol (7.0%), none developed sight-threatening retinopathy and 94% (165/175) remained without any retinopathy during pregnancy. Development of sight-threatening retinopathy was mainly observed in women with retinopathy in early pregnancy. Treatment for sight-threatening retinopathy was given to a minority (2.7 and 2.4%, respectively). Conclusion: Good glycaemic control and no retinopathy was seen in a large proportion of women in early pregnancy and none of these women developed sight-threatening retinopathy. The frequency of retinal screening can probably be safely reduced during pregnancy in these women.

Purpose: retinal vein occlusion (RVO) is classified as either branch (BRVO) or central (CRVO) RVO. The gold standard treatment for macular oedema (MO) secondary to RVO is intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections. Our study aimed to compare ranibizumab and aflibercept outcomes over a maximum follow-up of five years. Methods: this retrospective study assessed treatment-naïve RVO patients. Active disease was treated with three loading injections followed by a pro-re-nata (PRN) regimen of an anti-VEGF agent. Visual outcomes and injection frequency were analyzed, with patients stratified according to RVO subtype, anti-VEGF agent used, baseline vision, and age. Results: 316 CRVO-affected eyes and 467 BRVO-affected eyes were analysed. Visual benefits between different treatments did not significantly differ, except in year 1 in ranibizumab-treated BRVO eyes. However, aflibercept-treated CRVO and BRVO eyes required significantly fewer injections during the follow up period. Furthermore, our results confirm that younger patients achieve better visual outcomes with fewer intravitreal injections. Overall, half of our patients did not require further injections after 1 year from diagnosis. Conclusion: the results demonstrate that anti-VEGF treatment of RVO benefits vision for up to 5 years. Our findings are the first to suggest that compared to ranibizumab, fewer aflibercept injections may be required over five years follow up. Prospective randomised trials are needed to confirm this, alongside further attention to OCT scan features and the effect of patient demographics on treatment outcomes.

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

Introduction: To evaluate the short-term efficacy and safety of intravitreal dexamethasone implant (IDI) in patients with macular oedema associated with diabetic retinopathy (DR) and retinal vein occlusion (RVO) using enhanced-depth image optical coherence tomography (EDI-OCT) and to estimate the effect of dexamethasone on the choroid and the retinal vascular network using OCT angiography (OCTA). Methods: Fifteen eyes in 15 patients with macular oedema secondary to diabetes (DR, n = 8) or retinal vein occlusion (RVO, n = 7) were treated with intravitreal injection of sustained-release IDI. Primary efficacy end points were changes in best corrected visual acuity and central macular thickness (CMT). Secondary end points were changes in choroidal thickness and choroidal and retinal vascular networks as determined by OCTA. Results: CMT was significantly reduced from baseline by 3 h after injection (p < 0.01) and improved further during the 3-month follow-up. Visual acuity improvement was consistent with CMT reduction. No alterations in IOP or systemic side effects were observed. OCTA showed improvement from baseline in terms of decreased number and size of cysts and restoration of the retinal vascular network; flow choroidal thickness did not change significantly. CMT and visual acuity variations were similar in the two groups. Conclusions: CMT reduced as early as 3 h after the injection of IDI, with further reduction during follow-up. Choroidal thickness was unchanged, whereas the vascular retinal network improved from baseline to the end of study. Both EDI-OCT and OCTA were useful in demonstrating the early beneficial effects of IDI on the macula and the perifoveal vascular network. Funding: The article processing charges, the open access fee and the medical writing and editorial assistance was funded by Allergan.

Cataracts are one of the most common cause of blindness and visual impairment worldwide. However, very few people in Europe will go blind due to cataracts. In order to prevent blindness and visual impairment, more than 550 patients undergo cataract surgery every weekday in the Netherlands. Of these patients, 3.4% experience impaired recovery due to an accumulation of fluid in the retina, called pseudo-cystoid macular oedema. In a European multi-centre study among 1,100 patients, we researched the most effective treatment method for preventing macular oedema after cataract surgery. The most important results of this ESCRS PREMED study are described in this dissertation.

Cataracts are one of the most common cause of blindness and visual impairment worldwide. However, very few people in Europe will go blind due to cataracts. In order to prevent blindness and visual impairment, more than 550 patients undergo cataract surgery every weekday in the Netherlands. Of these patients, 3.4% experience impaired recovery due to an accumulation of fluid in the retina, called pseudo-cystoid macular oedema. In a European multi-centre study among 1,100 patients, we researched the most effective treatment method for preventing macular oedema after cataract surgery. The most important results of this ESCRS PREMED study are described in this dissertation.

Cavitations in the inner nuclear layer associated with severe optic atrophy and loss of retinal ganglion cells have clinically been termed microcystic macular oedema (MME). We describe a case series of MME in patients of all ages but predominantly younger patients with a wide range of optic atrophies ranging from acute onset optic disc drusen associated ischemic optic neuropathy to slowly progressive disease as glaucoma. There were no physical distinctions between MME in different causes of optic atrophy suggesting a common causative mechanism. We reviewed the literature on MME and it appears that MME is associated with more severe visual loss, and is more common in hereditary optic neuropathies and neuromyelitis optica spectrum disease rather than in patients with optic atrophy secondary to multiple sclerosis and glaucoma. Three main causative mechanisms have been proposed, including increased vitreal traction on the macular as the ganglion cells are lost. Others have suggested that trans-synaptic loss of cells in the inner nuclear layer causes formation of empty spaces or cavities. Finally, some have hypothesized a disturbance in the fluid homeostasis of the inner retina as Müller cells are lost or their function is impaired. There are no known treatments of MME. In conclusion, MME seems to be a marker of severe optic nerve atrophy irrespective of the underlying cause.

A cost analysis model was developed to evaluate the 3-year cost of treating vision impairment associated with chronic diabetic macular oedema (DMO) with either a single fluocinolone acetonide (FAc) implant or with 14 ranibizumab injections in the National Health Service (NHS) in England. The model accounts for the overall direct cost of treatment in both pseudophakic and phakic eyes including the cost of the drugs, the cost of administering the drugs, the cost of monitoring the patient, the cost of additional interventions required, and the cost of managing adverse events. The model indicates a considerable cost saving with the FAc implant irrespective of lens status even allowing for the additional cost of cataract extraction surgery in the majority of steroid-treated phakic patients. Using NHS list prices, the total treatment cost over a 3-year period for one eye is calculated to be £14,273 with multiple ranibizumab injections, £8205 with an FAc implant in a pseudophakic eye and £8932 with an FAc implant in a phakic eye – resulting in an overall cost saving with the implant of £6068 per pseudophakic eye and £5341 per phakic eye. The FAc implant remains the dominant treatment when up to 60% of patients receive the FAc implant and at least 40% of patients receive 14 ranibizumab injections. The results presented here indicate that 3 years of treatment with a single FAc implant offers a considerable cost saving over 3 years of treatment with ranibizumab (assumed to comprise 14 injections) in both phakic and pseudophakic eyes.

A cost analysis model was developed to evaluate the 3-year cost of treating vision impairment associated with chronic diabetic macular oedema (DMO) with either a single fluocinolone acetonide (FAc) implant or with 14 ranibizumab injections in the National Health Service (NHS) in England. The model accounts for the overall direct cost of treatment in both pseudophakic and phakic eyes including the cost of the drugs, the cost of administering the drugs, the cost of monitoring the patient, the cost of additional interventions required, and the cost of managing adverse events. The model indicates a considerable cost saving with the FAc implant irrespective of lens status even allowing for the additional cost of cataract extraction surgery in the majority of steroid-treated phakic patients. Using NHS list prices, the total treatment cost over a 3-year period for one eye is calculated to be £14,273 with multiple ranibizumab injections, £8205 with an FAc implant in a pseudophakic eye and £8932 with an FAc implant in a phakic eye – resulting in an overall cost saving with the implant of £6068 per pseudophakic eye and £5341 per phakic eye. The FAc implant remains the dominant treatment when up to 60% of patients receive the FAc implant and at least 40% of patients receive 14 ranibizumab injections. The results presented here indicate that 3 years of treatment with a single FAc implant offers a considerable cost saving over 3 years of treatment with ranibizumab (assumed to comprise 14 injections) in both phakic and pseudophakic eyes.

Purpose: Floaters caused by degenerative or postoperative changes in the vitreous can interfere with all aspects of visual functioning. The aim of this study is to report the longterm outcome of pars plana vitrectomy (PPV) for persistent vitreous opacities. Methods: In a retrospective, non-randomized, interventional case study we reviewed all cases of vitreous floaters that were vitrectomized at our department between 1997 and 2006. Patient complaints and satisfaction were assessed by a questionnaire administered at the end of follow-up. Results: Seventy-three consecutive cases were included (61 patients). Mean Snellen best corrected visual acuity (BCVA) before surgery was 0.81. Overall, 85% of patients complained of severe or very severe difficulty caused by floaters. A total of 42% of eyes were pseudophakic, four of which were operated with combined PPV and phacoemulsification. Mean follow-up time was 37 months. Of the phakic eyes, 60% were operated for cataract during follow-up. One retinal detachment (RD) occurred immediately postoperatively (1.3%) and another four eyes developed RD during longterm follow-up 24-44 months after PPV (5.5% of cases). Postoperative BCVA remained mostly unchanged. Overall, 88% of patients were satisfied with the results of the operation. Conclusions: Some patients make considerable complaints as a result of vitreous opacities and their distress does not correlate with visual acuity. Vitrectomy is a safe and effective procedure with which to help these patients. Patients should be informed about the risk of cataract progression, unexpected inflammatory reaction and an increased risk for RD several years after PPV (5.5%).

PURPOSE: Floaters caused by degenerative or postoperative changes in the vitreous can interfere with all aspects of visual functioning. The aim of this study is to report the longterm outcome of pars plana vitrectomy (PPV) for persistent vitreous opacities. METHODS: In a retrospective, non-randomized, interventional case study we reviewed all cases of vitreous floaters that were vitrectomized at our department between 1997 and 2006. Patient complaints and satisfaction were assessed by a questionnaire administered at the end of follow-up. RESULTS: Seventy-three consecutive cases were included (61 patients). Mean Snellen best corrected visual acuity (BCVA) before surgery was 0.81. Overall, 85% of patients complained of severe or very severe difficulty caused by floaters. A total of 42% of eyes were pseudophakic, four of which were operated with combined PPV and phacoemulsification. Mean follow-up time was 37 months. Of the phakic eyes, 60% were operated for cataract during follow-up. One retinal detachment (RD) occurred immediately postoperatively (1.3%) and another four eyes developed RD during longterm follow-up 24-44 months after PPV (5.5% of cases). Postoperative BCVA remained mostly unchanged. Overall, 88% of patients were satisfied with the results of the operation. CONCLUSIONS: Some patients make considerable complaints as a result of vitreous opacities and their distress does not correlate with visual acuity. Vitrectomy is a safe and effective procedure with which to help these patients. Patients should be informed about the risk of cataract progression, unexpected inflammatory reaction and an increased risk for RD several years after PPV (5.5%).

Purpose: To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC), who were treated with intravitreal bevacizumab injection. Methods: Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. VEGF concentration in the vitreous fluid was measured by ELISA in one of these patients. Results: Case 1. 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema was resolved by intravitreal injection of bevacizumab. Case 2. 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed the neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size markedly reduced with regression of neovascularization. Conclusions: These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC.

Purpose: To describe two patients with macular oedema secondary to tuberous sclerosis complex (TSC), who were treated with intravitreal bevacizumab injection. Methods: Interventional case reports. Bevacizumab 1.25 mg was injected into the vitreous of two patients with TSC-associated macular oedema / exudative retinal detachment. VEGF concentration in the vitreous fluid was measured by ELISA in one of these patients. Results: Case 1. 22-year-old woman with TSC was diagnosed as having multiple retinal hamartomas in both eyes. Eleven years later, the patient developed macular oedema with epiretinal membrane formation in the right eye. The patient underwent pars plana vitrectomy with retinal photocoagulation for retinal tumours. VEGF concentration in the vitreous fluid was high compared to that in patients without retinal vascular diseases. Recurrent macular oedema was resolved by intravitreal injection of bevacizumab. Case 2. 32-year-old woman with TSC-associated retinal hamartoma, temporally showing macular exudative retinal detachment, developed the neovascularization originated from the tumour. By intravitreal bevacizumab injection, the tumour size markedly reduced with regression of neovascularization. Conclusions: These results suggest that VEGF derived from retinal hamartomas causes macular oedema associated with TSC. Intravitreal injections of bevacizumab may be a useful therapeutic option for macular oedema secondary to TSC.

PURPOSE: To evaluate the efficacy of flicker perimetry compared with that of static perimetry in determining central visual field losses in participants with type 2 diabetes mellitus. METHODS: Flicker and static perimetry were performed using the Medmont field analyser on 20 participants with type 2 diabetes mellitus and 24 age-matched control participants. RESULTS: Flicker, but not static, perimetry demonstrated significant reductions in thresholds in those participants who had a recent diagnosis of diabetes or who had no or only minimal diabetic retinopathy compared to the control group at eccentricities close to fixation. CONCLUSION: Flicker perimetry is recommended for the evaluation of visual field losses in participants with recent onset of diabetes and minimal diabetic retinopathy.

Aims: Psychophysical tests such as Letter contrast sensitivity (CS) and flicker perimetry have been used to detect early functional losses in ocular disease such as age-related maculopathy (ARM) and in vascular disorders such as migraine. This study set out to determine the ability of these tests to detect early functional losses in type 2 diabetics with minimal or early diabetic retinopathy (DR). Methods: Subjects consisted of 20 patients with type 2 diabetes (duration, following diagnosis, ranging from 6 months to 18 years) and 24 age-matched normal controls. Letter CS, using the Pelli-Robson cha.ii, visual acuity (VA) using the standard high contrast Bailey-Lovie chart and monocular visual fields (VF) were measured. Static and flicker VF were measured using the Medmont M600 perimeter (MFA) and SIT A-standard fields using the Humphrey Field Analyser (HFA) were tested. Results: Letter CS was able to discriminate those diabetic subjects with none or early DR and those with and without ME from the control group, whereas VA was not able to detect any significant differences in visual function in these diabetic sub-groups compared to the control group. In terms of visual fields, both the pattern defect (PD) index and hill-ofvision profiles were analysed. In those with early onset of diabetes and in those with none/minimal DR, only the PD index obtained with the flicker technique was significantly worse than the control group. The hill-of-vision profiles showed that the PD loss in those with minimal DR when flicker perimetry was used, was due to a central depression close to fixation, whereas the MFA static and HFA profiles consisted of a general depression across the field. This indicated that the flicker technique is a more sensitive test than the static technique in determining central visual field defects in those with minor observable retinal changes. The inability of the HFA to detect changes to the macula region was thought to be due to the large grid spacing of