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Purpose: To review the risk of systemic adverse events and all-cause mortality following same-day bilateral anti-VEGF injections., Methods: Twelve literature databases were searched for studies on same-session bilateral intravitreal anti-VEGF injections. Studies reporting on systemic adverse events and mortality were included. Data extraction was made independently by two authors and discussed afterwards until consensus was reached., Results: Seven studies were included with a total of 13,406 intravitreal anti-VEGF injections (6703 bilateral injections sessions) given to 689 patients. Across all studies, mean age of patients ranged from 55.7 to 82.5 years, and mean follow-up times ranged from 1.3 to 41 months. Six studies reported on systemic adverse events: Two cases of non-fatal cardiac adverse events were reported after 12,964 injections (6482 bilateral injection sessions) in 626 patients. Four studies reported on death: 12 deaths were recorded after 6233 bilateral injection sessions in a total population of 554 subjects., Conclusions: We suggest that the risk of non-fatal systemic adverse events and death after same-session bilateral anti-VEGF injection is reasonably low, but larger studies with follow-ups of several years are needed to quantify the exact risk., Study Registration: Prospectively registered in PROSPERO, registration ID: CRD42023428254, registration date: 20/05/2023., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To report short-term outcomes of treatment switch to faricimab in real-world patients with aflibercept-resistant neovascular age-related macular degeneration (AMD)., Methods: Single-center, retrospective cohort study with chart-review using electronic injection database, electronic medical records, and optical coherence tomography (OCT) data from May to September 2023., Results: A total of 50 eyes of 46 patients were analyzed. Faricimab treatment led to absence of fluid in 32% of the eyes and a reduction of fluid in 84% of the eyes. There was a statistically significant decrease in central retinal thickness (CRT) and pigment epithelial detachment (PED) height in those that responded to the switch (median difference: - 31 μm, IQR: 55, p < 0.0001 and median difference: - 21 μm, IQR: 36, p < 0.0001, respectively) and a statistically significant increase in CRT (median difference: + 19 μm, IQR: 20, p = 0.0143) and no change in PED height (median difference: + 22 μm, IQR: 64, p = 0.1508) in those that did not. Best-corrected visual acuity (BCVA) showed marginal decrease with low statistical significance. No ocular or systemic safety events were observed., Conclusions: Our findings suggest that switching to faricimab is generally safe and effective in patients with neovascular AMD who are otherwise difficult to treat and have residual fluid despite frequent injections with aflibercept. We observed a high rate of morphological response to the treatment switch, improvement of anatomical parameters with about one-third of patients having dry macula following a single injection, and a marginal change in BCVA. Sustainability of these results requires further investigation., Study Registration: ClinicalTrials.gov registration number: NCT06124677. Date of registration: 09/11/2023, retrospectively registered., (© 2024. The Author(s).)

Purpose: To investigate ocular and systemic factors associated with the retinal arterial wall-to-lumen ratio (WLR) and to determine the relative contribution of genetic and environmental variation to WLR in healthy adults., Methods: This cross-sectional twin study included 78 monozygotic and 67 dizygotic same-sex twin pairs aged 58.4 ± 9.8 (mean ± SD) years. Lumen diameter (LD) and outer diameter (OD) of a superotemporal retinal artery were measured using adaptive optics fundus photography, and the WLR was calculated. Linear mixed model regression analysis of associations with WLR comprised the descriptive variables ocular axial length (AL), intraocular pressure (IOP), height, weight, body mass index (BMI), smoking, blood pressure, high density (HDL), low density (LDL) and very low density (VLDL) lipoproteins, total cholesterol and triglycerides. The relative influence of genes and environment on WLR was calculated through polygenetic modelling., Results: Increasing age and arterial blood pressure were associated with a higher WLR, while increasing retinal artery OD and ocular AL were associated with a lower WLR. Sex, smoking status, BMI, IOP, cholesterol levels or triglycerides had no detectable impact on the WLR. Broad-sense heritability of WLR was 21% (95% CI: 1-41%), while environmental factors accounted for the remaining 79% of the interindividual variance (95% CI: 59-99%)., Conclusion: Retinal artery wall thickness was closely linked to increasing age and higher arterial blood pressure, the latter being mediated by the environment over genes., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics., Methods: In this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at -80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h 2 ) of cytokine concentrations was analyzed., Results: 90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h 2 >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h 2  = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1β (82.2%) and monocyte chemoattractant protein 1 (68.2%)., Conclusions: The tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease., Competing Interests: Declaration of competing interest The authors have no commercial relations with the suppliers of diagnostic devices or therapeutics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Concerns related to pain from intravitreal injections are one of the key factors mentioned by patients when asked about therapy. In this systematic review and network meta-analysis, we evaluate the literature of comparative clinical trials on the relationship between needle gauge size and pain experience during intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy., Methods: We searched 12 literature databases on 14 October 2023 for comparative studies of gauge sizes for intravitreal anti-VEGF injections. The primary outcome of interest was the reported pain experience immediately after the injection. All outcomes of pain were transformed into standardized effect sizes using Cohen's d. Using a network meta-analysis approach, we were able to compare all gauge sizes and rank them according to the reported pain experience., Results: We identified nine eligible studies with data on a total of 998 patients and 1004 eyes. Needle sizes studied were 26-gauge, 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge. A complete network was present, which allowed for a network meta-analysis. We used the thickest (26-gauge) needle as the reference group and observed a clear trend of lower pain experience with thinner gauge sizes (d: -0.4, d: -2.7, d: -3.8, d: -4.8, d: -4.5, and d: -5.3; respectively, for 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge)., Conclusion: A gauge size of 30 or thinner may minimize patient discomfort related to intravitreal anti-VEGF therapy., (© 2024. The Author(s).)

Purpose: To review the risk of endophthalmitis in same-day bilateral anti-VEGF injections., Methods: We searched 12 literature databases for studies on the risk of endophthalmitis after same-day bilateral intravitreal anti-VEGF injections. Data extraction was made independently by two authors and discussed afterward until reaching consensus., Results: Seventeen studies were included with a total of 138,478 intravitreal anti-VEGF injections (69,239 bilateral injections sessions) given in at least 7579 patients. In total, 33 cases of endophthalmitis had occurred, and no cases were bilateral. The incidence of endophthalmitis ranged from 0 to 0.53% per intravitreal injection across studies., Conclusions: We suggest that clinicians can consider same-day treatment of both eyes of patients in need of bilateral intravitreal anti-VEGF injection therapy, but larger studies are needed to quantify the exact risk of endophthalmitis., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Importance: Since bilateral simultaneous postoperative endophthalmitis (BSPOE) after immediate sequential bilateral cataract surgery (ISBCS) can be devastating for the patient, evaluating such cases in depth is important to maintaining patient safety., Objective: To evaluate whether a systemic breach of sterility was associated with an outbreak of BSPOE after ISBCSs performed on the same day at a single community-based eye clinic., Design, Setting, and Participants: This retrospective case series included all patients diagnosed with BSPOE at ophthalmology departments in Denmark following an infectious outbreak after ISBCSs performed at a single community-based eye clinic in December 2022., Exposure: Bilateral simultaneous postoperative endophthalmitis acquired after ISBCS., Main Outcome and Measures: Patient recovery from BSPOE after ISBCS was evaluated based on clinical and microbiological reports., Results: A woman aged 71 years, a man aged 84 years, and a woman aged 79 years consecutively presented with symptoms of endophthalmitis at regional eye departments 4 to 8 days after ISBCS performed on the same date at the same eye clinic. Five of 6 infected eyes underwent vitrectomy, and all eyes received an intravitreous injection of antibiotics. The same strain of Staphylococcus epidermidis was isolated in 4 of 5 eyes that underwent vitrectomy. Contamination of viscoelastics was ruled out with repeated cultures. One eye was eviscerated due to phthisis. In another patient, the final visual acuity of the eye most severely affected was 20/63 Snellen equivalents. Visual acuity of the remaining eyes recovered to 20/25 (3 eyes in 2 patients) and 20/20 (1 eye) Snellen equivalents., Conclusions and Relevance: The finding of the same strain of S epidermidis in all patient cultures suggests a systemic breach of sterility at the clinic on the day of ISBCS. The outcome of these cases emphasizes the need to adhere to a strict surgical methodology and sterile principles during ISBCS.

Importance: Patients with nonneovascular age-related macular degeneration (AMD) are encouraged to use the Amsler grid test for self-assessment to facilitate early diagnosis. The test is widely recommended, suggesting a belief that it signals worsening AMD, warranting its use in home monitoring., Objective: To systematically review studies of the diagnostic test accuracy of the Amsler grid in the diagnosis of neovascular AMD and to perform diagnostic test accuracy meta-analyses., Data Sources: A systematic literature search was conducted in 12 databases for relevant titles from database inception until May 7, 2022., Study Selection: Studies included those with groups defined as having (1) neovascular AMD and (2) either healthy eyes or eyes with nonneovascular AMD. The index test was the Amsler grid. The reference standard was ophthalmic examination. After removal of obviously irrelevant reports, 2 authors (J.B. and M.S.) independently screened the remaining references in full text for potential eligibility. Disagreements were resolved by a third author (Y.S.)., Data Extraction and Synthesis: Two authors (J.B. and I.P.) independently extracted all data and evaluated quality and applicability of eligible studies using the Quality Assessment of Diagnostic Accuracy Studies 2. Disagreements were resolved by a third author (Y.S.)., Main Outcomes and Measures: Sensitivity and specificity of the Amsler grid for detecting neovascular AMD with comparators being either healthy control participants or patients with nonneovascular AMD., Results: Of 523 records screened, 10 studies were included with a total of 1890 eyes (mean participant age ranging from 62 to 83 years). Sensitivity and specificity to diagnose neovascular AMD were 67% (95% CI, 51%-79%) and 99% (95% CI, 85%-100%), respectively, when comparators were healthy control participants and 71% (95% CI, 60%-80%) and 63% (95% CI, 49%-51%), respectively, when control participants were patients with nonneovascular AMD. Overall, potential sources of bias were low across studies., Conclusions and Relevance: Although the Amsler grid is easy and inexpensive to use for detection of metamorphopsia, its sensitivity may be at levels typically not recommended for monitoring. Coupling this lower sensitivity with only moderate specificity to identify neovascular AMD in a population at risk, these findings suggest that such patients typically should be encouraged to undergo ophthalmic examination regularly, regardless of any results of Amsler grid self-assessment.

Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short-term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta-analyses to compare to non-treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half-dose or half-fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half-dose or half-fluence PDT (OR: 20.6; 95% CI: 6.3-66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0-655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7-6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best-corrected visual acuity was only obtained by half-dose/-fluence PDT (-0.13 logMAR; 95% CI: -0.20 to -0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half-dose/-fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long-term data available for PDT-based treatments finding persisting treatment results, half-dose or half-fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The purpose of this study was to examine the ocular and systemic risk profile of the fundus phenotype ≥ 20 small hard (macular) drusen (< 63 μm in diameter)., Methods: This single-center, cross-sectional study of 176 same-sex twin pairs aged 30 to 80 (median 60) years was a component of a framework study of the transition from not having age-related macular degeneration to having early AMD. Drusen categories assessed using fundus photography and optical coherence tomography included small hard drusen (diameter < 63 μm), intermediate soft drusen (63-125 μm), and large soft drusen (> 125 μm), of which the soft drusen are compatible with a diagnosis of AMD., Results: Having ≥ 20 small hard drusen within or outside the macula was associated with increasing age, lower body mass index, shorter axial length, hyperopia, female sex, increasing high-density lipoprotein (HDL), high alcohol consumption, and with the presence of soft drusen., Conclusions: Having ≥ 20 small hard drusen was associated with some AMD-related risk factors, but not with smoking, increasing body mass index, and higher blood pressure. Having ≥ 20 small hard drusen was also associated with soft drusen, in agreement with previous studies. These findings suggest that small hard drusen are not an early manifestation of AMD but the product of a distinct process of tissue alteration that promotes the development of AMD or some subtype thereof., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Belmouhand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort., Methods: This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location., Results: The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 μm), ≥20 small hard extramacular drusen, intermediate drusen (63-125 μm) anywhere, and large drusen (>125 μm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier., Conclusion: Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Deep optic disc drusen (ODD) are located below Bruch's membrane opening (BMO) and may go undetected due to the challenges in imaging them. The purpose of this study is a head-to-head comparison of currently widely used imaging technologies: swept-source optical coherence tomography (SS-OCT; DRI OCT-1 Triton, Topcon) and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT; Spectralis OCT, Heidelberg Engineering) for the detection of deep ODD and associated imaging features. The eyes included in this study had undergone high-resolution imaging via both EDI SD-OCT and SS-OCT volume scans, which showed at least one deep ODD or a hyperreflective line (HL). Grading was performed by three graders in a masked fashion. The study findings are based on 46 B-scan stacks of 23 eyes including a total of 7981 scans. For scan images with ODD located above or below the level of BMO, no significant difference was found between the two modalities compared in this study. However, for HLs and other features, EDI SD-OCT scan images had better visualization and less artifacts. Although SS-OCT offers deep tissue visualization, it did not appear to offer any advantage in ODD detection over a dense volume scan via EDI SD-OCT with B-scan averaging.

Purpose: Intravitreal injections and cataract surgery are two common procedures in the elderly. Posterior capsular rupture (PCR) is a rare but important complication of cataract surgery. We systematically reviewed the literature on previous intravitreal injections as a risk factor of PCR and performed meta-analyses to provide pooled summary risk estimates., Methods: We searched 13 literature databases on 1 June 2021 for studies evaluating the risk of PCR in eyes undergoing cataract surgery with data on previous intravitreal injections. Data extraction was made independently by two authors and discussed afterwards until reaching consensus. Random effects meta-analyses on the pooled odds ratio (OR) of PCR in eyes with previous intravitreal injections were made using MetaXL 5.3., Results: Six studies on 1 051 097 eyes undergoing cataract surgery were eligible for the qualitative and quantitative review. Previous history of intravitreal injections was present in 7034 eyes (majority was anti-VEGF). Our meta-analyses revealed that any previous intravitreal injection was a risk factor for PCR with an OR of 2.30 (95% CI 1.39-3.81). For each previous intravitreal injection, the risk of PCR was OR 1.04 (95% CI 1.01-1.08) (equivalent of relative risk ~1.04). In other words, risk of PCR increases by 4% for each previous intravitreal injection., Conclusions: Previous intravitreal injection is a risk factor for PCR and should be taken into account when planning cataract surgery. However, to be regarded as a clinically significant risk of PCR, a substantial number of previous intravitreal injection (e.g. ≥10) should have been administered, considering that the a priori risk of PCR is very low (~1%)., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

The blue-green autofluorescence of the ocular lens increases with age, glycemia and smoking, as the irreplaceable structural proteins of the lens slowly accumulate damage from the encounter with reactive molecular species. We have conducted a prospective study of lens autofluorescence over two decades in a twin cohort. The study included 131 phakic, non-diabetic adult twins (median age at follow-up 58 years, range 41-66 years) who were examined twice at an interval of 21 years. Change in anterior lens peak autofluorescence was analyzed in relation to age, current and baseline glycemia, cumulative smoking and heritability. The level of lens autofluorescence in the study population increased as a function of age and smoking (p ≤.002), but not as a function of glycemia (p ≥.069). Lens autofluorescence remained a highly heritable trait (90.6% at baseline and 93.3% at follow-up), but whereas the combined effect of age and cumulative smoking explained 57.2% of the variance in lens autofluorescence at baseline in mid-life, it only accounted for 31.6% at follow-up 21 years later. From mid to late adulthood, the level of blue-green fluorescence remained overwhelmingly heritable, but became less predictable from age, smoking habits and glycemic status. Presumably, as the lens ages, its intrinsic characteristics come to dominate over environmental and systemic factors, perhaps in a prelude to the development of cataract., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To explore subretinal fluid (SRF) morphology in chronic central serous chorioretinopathy (cCSC) after one session of either high-density subthreshold micropulse laser (HSML) treatment or half-dose photodynamic therapy (PDT)., Methods: We retrospectively obtained optical coherence tomography (OCT) scans from a subset of patients from a randomized controlled trial on treatment-naïve eyes with cCSC allocated to either HSML treatment or half-dose PDT. OCT scans were evaluated prior to treatment and 6-8 weeks post-treatment, where we measured maximum SRF height and width, calculated the maximum height-to-maximum width-ratio (maxHWR) and calculated the total SRF volume., Results: Forty-one eyes of 39 cCSC patients were included. SRF morphology ranged from flat to dome-shaped, quantified as maxHWR ranging between 0.02 and 0.12. SRF volume was median 0.373 μl (range: 0.010-4.425 μl) and did not correlate to maxHWR (rho = -0.004, p = 0.982). Half-dose PDT was superior to HSML treatment in complete SRF resolution (RR = 3.28, p = 0.003) and in morphological changes of SRF (Δ maximum height , p = 0.001; Δ maximum width , p < 0.001; Δ volume , p = 0.025). SRF resolved completely in 19/22 PDT-treated eyes (86%) and 5/19 HSML-treated eyes (26%). SRF volume increased in five eyes (26%) after HSML treatment, and in none of the eyes after half-dose PDT. SRF morphology at baseline did not predict treatment outcomes., Conclusion: SRF morphology changed after both HSML treatment and half-dose PDT in cCSC, with SRF disappearing in most PDT-treated patients, whereas SRF volume increased in a sizeable proportion of HSML-treated patients. Baseline SRF characteristics measured in this study were unable to predict outcomes after either HSML treatment or half-dose PDT., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Introduction: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 μm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort., Methods: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 μm, or (4) ≥20 small hard drusen combined with drusen ≥63 μm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects., Results: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 μm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 μm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 μm at follow-up (p = 0.02). Development of drusen ≥63 μm was attributable to 49% genetic effects and 51% environmental effects., Conclusion: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 μm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 μm at baseline was associated with incident drusen ≥63 μm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Lens and skin fluorescence are related to the systemic accumulation of advanced glycation end products, which is accelerated in diabetes. We have examined lens fluorescence and skin fluorescence in healthy adult twins. The study enrolled twins aged median 59 years from a national population-based registry. Diabetic individuals were excluded from analysis. The interrelatedness between fluorescence parameters and relations between fluorescence and age, current HbA1c and smoking pack years were examined using correlation tests and mixed model linear regression analyses. Broad-sense heritability was analyzed and compared for lens fluorescence, skin fluorescence and HbA1c. Lens fluorescence and skin fluorescence were crudely interrelated (R = 0.38). In linear regression analyses, age explained a larger fraction of the variance in lens fluorescence (R2 = 32%) than in skin fluorescence (R2 = 20%), whereas HbA1c explained smaller variance fractions (R2 = 3% and 8%, respectively) followed by smoking pack years (4% and 3%, respectively). In multivariate analyses, age, HbA1c and smoking pack years combined explained more of the variance in lens fluorescence (R2 = 35%) than in skin fluorescence (R2 = 21%), but the influence of HbA1c on lens fluorescence was not statistically significant (p = .2). Age-adjusted broad-sense heritability was 85% for lens fluorescence, 53% for skin fluorescence and 71% for HbA1c in best fitting heritability models. Both fluorescence parameters increased with age, current glycemia and cumulative smoking. Lens fluorescence was found to be a predominantly heritable trait, whereas skin fluorescence was more influenced by environmental factors and closer related to current glycemia. The results suggest that skin fluorophores have a faster turn-over than lens fluorophores., Competing Interests: The authors have declared that no competing interests exist.