***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: To evaluate macular thickness in eyes with mild nonproliferative diabetic retinopathy ( NPDR ) , patients with diabetes type 2 , NPDR level 20 or 35 , and without evidence of clinical macular edema underwent best-corrected visual acuity assessment , color fundus photography and Stratus optical coherence tomography .  Mean center point thickness ( CPT ) and mean central subfield ( CSF ) thickness were compared with those of a healthy control population . 410 eyes/ patients aged 61.2 ± 8.3 years , and with glycosylated hemoglobin of 7.9 ± 1.5 % were included . Mean CPT and CSF were 186.6 ± 28.4 and 215.2 ± 25 µm , respectively , significantly increased compared to healthy subjects ( p < 0.001 ) . CSF thickness was abnormally increased in 17.6 % of the patients , with values within the normal range in 79.5 % , and abnormally decreased in 2.9 % . CPT and CSF thickness were significantly thicker in men . No systemic factors showed a significant association . A significant increase in the macular thickness was found in eyes/ patients with mild NPDR without clinical macular edema ; however , only 17.6 % of the eyes/ patients had abnormally increased values and less than 3 % abnormally decreased values Optical coherence tomography ( OCT ) has been proven useful in measuring retinal thickness ( RT ) in patients with diabetes , although with discordant results in different studies . We examined RT in patients with type 1 diabetes ( T1D ) with or without minimal diabetic retinopathy ( MDR ) to test whether OCT is able to identify early retinal changes and potential correlations with metabolic parameters . RT of 102 patients with T1D ( 53 females , 49 males , aged 27.03 ± 7.4 years ) and of 42 healthy controls was examined , with analysis of nine different sectors ( fovea , four peri central and four peripheral sectors ) . According to the results of basal fundus photography , patients were divided into two groups , without MDR ( 48 cases ) and with MDR ( 54 cases ) . Patients with proliferative DR or macular edema were excluded . No difference was found between patients with or without MDR and the control group for all OCT parameters investigated . Mean HbA1c of the last 5 years ( P < 0.001 ) , microalbuminuria ( P = 0.002 ) , total ( P = 0.046 ) and LDL cholesterol ( P = 0.007 ) and triglyceride ( P < 0.001 ) levels were higher in patients with MDR , along with higher prevalence of hypertension ( P = 0.013 ) , younger age at diagnosis ( P = 0.018 ) and longer diabetes duration ( P < 0.001 ) with regard to the patients without MDR and controls , although no significant correlation between these parameters and RT was found . Our study suggests that MDR without macular edema in patients with T1D can not be detected with OCT . Therefore , the conventional diagnostic methods are m and atory to detect early DR AIMS Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy . We present the baseline findings of the ' Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers'(L AND Mark ) study . METHODS The L AND Mark study is a 4-year , two-site , natural history study of three participant groups : type 1 diabetes with neuropathy ( T1W ) , type 1 diabetes without neuropathy ( T1WO ) and control participants without diabetes or neuropathy . All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry . RESULTS 76 T1W , 166 T1WO and 154 control participants were enrolled into the study .  Corneal sensation threshold was significantly higher ( i.e. , sensitivity was lower ) in T1W ( 1.0±1.1mbars ) than T1WO ( 0.7±0.7mbars ) and controls ( 0.6±0.4mbars ) ( p<0.001 ) , with no difference between T1WO and controls . Corneal nerve fibre length was lower in T1W ( 14.0±6.4mm/mm(2 ) ) compared to T1WO ( 19.1±5.8mm/mm(2 ) ) and controls ( 23.2±6.3mm/mm(2 ) ) ( p<0.001 ) . Corneal nerve fibre length was lower in T1WO compared to controls . CONCLUSIONS The L AND Mark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy . However , corneal nerve fibre length is reduced in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy PURPOSE Optical coherence tomography ( OCT ) is a new technology that uses near-infrared light in an interferometer to produce approximately 10-microns resolution cross-sectional images of the tissue of interest . The authors performed repeated quantitative assessment of nerve fiber layer thickness in individuals with normal and glaucomatous eyes , and they evaluated the reproducibility of these measurements . METHODS The authors studied 21 eyes of 21 subjects by OCT .  Each subject underwent five repetitions of a series of scans on five separate occasions within a 1-month period . Each series consisted of three circular scans around the optic nerve head ( diameters , 2.9 , 3.4 , and 4.5 mm ) . Each series was performed separately using internal ( fixation with same eye being studied ) and external ( fixation with contralateral eye ) fixation techniques . The eye studied and the sequence of testing were assigned r and omly . RESULTS Internal fixation ( IF ) , in general , provides a slightly higher degree of reproducibility than external fixation ( EF ) . Reproducibility was better in a given eye on a given visit than from visit to visit . Reproducibility as measured by intraclass correlation coefficients were as follows : circle diameter ( CD ) , 2.9 mm , 0.51/0.57 ( normal/glaucoma ) ( IF ) , 0.43/0.54 ( EF ) ; CD , 3.4 mm , 0.56/0.52 ( IF ) , 0.43/0.61 ( EF ) ; CD , 4.5 mm , 0.53/0.43 ( IF ) , 0.42/0.49 ( EF ) . CONCLUSIONS Nerve fiber layer thickness can be reproducibly measured using OCT . Internal is superior to external fixation ; each circle diameter tested provides adequate reproducibility We sought to determine whether early nerve damage may be detected by corneal confocal microscopy ( CCM ) , skin biopsy , and neurophysiological tests  in 86 recently diagnosed type 2 diabetic patients compared with 48 control subjects .  CCM analysis using novel algorithms to reconstruct nerve fiber images was performed for all fibers and major nerve fibers ( MNF ) only .  Intraepidermal nerve fiber density ( IENFD ) was assessed in skin specimens . Neurophysiological measures included nerve conduction studies ( NCS ) , quantitative sensory testing ( QST ) , and cardiovascular autonomic function tests ( AFTs ) . Compared with control subjects , diabetic patients exhibited significantly reduced corneal nerve fiber length ( CNFL-MNF ) , fiber density ( CNFD-MNF ) , branch density ( CNBD-MNF ) , connecting points ( CNCP ) , IENFD , NCS , QST , and AFTs . CNFD-MNF and IENFD were reduced below the 2.5th percentile in 21 % and 14 % of the diabetic patients , respectively . However , the vast majority of patients with abnormal CNFD showed concomitantly normal IENFD and vice versa . In conclusion ,  CCM  and skin biopsy both detect nerve fiber loss in recently diagnosed type 2 diabetes , but largely in different patients , suggesting a patchy manifestation pattern of small fiber neuropathy . Concomitant NCS impairment points to an early parallel involvement of small and large fibers , but the precise temporal sequence should be clarified in prospect i ve studies IMPORTANCE Microglia have been associated with inflammatory changes underlying diabetic retinopathy . OBJECTIVE To investigate whether low-dose oral doxycycline monohydrate , a drug capable of inhibiting microglial activation , can improve or slow the deterioration of retinal function and whether it can induce regression or slow progression of diabetic retinopathy in patients with mild to moderate nonproliferative diabetic retinopathy ( NPDR ) . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-masked , 24-month proof-of-concept clinical trial . We r and omized 33 patients ( from the Penn State Hershey Eye Center ) with at least 1 eye with mild to moderate NPDR ( Early Treatment Diabetic Retinopathy Study level 20 - 43 ) to doxycycline monohydrate , 50 mg/d , or daily placebo for 24 months . MAIN OUTCOMES AND MEASURES Mean change at 24 months compared with baseline in the foveal sensitivity of matrix frequency-doubling perimetry in each treatment group . We also compared the 2 groups with respect to change from baseline to 24 months in functional variables ( Humphrey photopic visual field testing using the Swedish interactive thresholding algorithm 24 - 2 strategy , contrast sensitivity , dark adaptation , visual acuity , and quality of life ) and anatomical variables ( diabetic retinopathy severity level , area of retinal thickening , central subfield thickness on optical coherence tomography , and macular volume on optical coherence tomography ) . RESULTS From baseline to month 24 , no significant difference was detected between groups with respect to all visual function and anatomical outcomes assessed . CONCLUSIONS AND RELEVANCE Although a link between low-dose oral anti-inflammatory agents and sub clinical improvement in inner retinal function has been suggested in patients with severe NPDR or non-high-risk proliferative diabetic retinopathy , the same association was not found in the present study of patients with mild to moderate NPDR . The different findings in the 2 patient population s may relate to a differential effect of doxycycline on different stages of diabetic retinal dysfunction , or the sample size of the present study may be too small to detect a treatment effect of doxycycline in patients with mild to moderate NPDR . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00917553 OBJECTIVE We aim ed to determine the corneal confocal microscopy ( CCM ) parameter that best identifies  diabetic sensorimotor polyneuropathy ( DSP ) in type 1 diabetes and to describe its performance characteristics . RESEARCH DESIGN AND METHODS Concurrent with clinical and electrophysiological examination for classification of DSP , CCM was performed on 89 type 1 diabetic and 64 healthy subjects to determine  corneal nerve fiber length ( CNFL ) , density , tortuosity , and branch density . Area under the curve ( AUC ) and optimal thresholds for DSP identification in those with diabetes were determined by receiver operating characteristic ( ROC ) curve analysis . RESULTS DSP was present in 33 ( 37 % ) subjects . With the exception of tortuosity , CCM parameters were significantly lower in DSP case subjects . In ROC curve analysis , AUC was greatest for CNFL ( 0.88 ) compared with fiber density ( 0.84 , P = 0.0001 ) , branch density ( 0.73 , P < 0.0001 ) , and tortuosity ( 0.55 , P < 0.0001 ) . The threshold value that optimized sensitivity and specificity for ruling in DSP was a CNFL of ≤14.0 mm/mm2 ( sensitivity 85 % , specificity 84 % ) , associated with positive and negative likelihood ratios of 5.3 and 0.18 . An alternate approach that used separate threshold values maximized sensitivity ( threshold value ≥15.8 mm/mm2 , sensitivity 91 % , negative likelihood ratio 0.16 ) and specificity ( ≤11.5 mm/mm2 , specificity 93 % , positive likelihood ratio 8.5 ) . CONCLUSIONS Among CCM parameters , CNFL best discriminated DSP cases from control subjects . A single threshold offers clinical ly acceptable operating characteristics , although a strategy that uses separate thresholds to respectively rule in and rule out DSP has excellent performance while minimizing unclassified subjects . We hypothesize that values between these thresholds indicate incipient nerve injury that represents those individuals at future neuropathy risk Purpose . To evaluate macular thickness , agreement , and intraclass repeatability in three optical coherence tomography ( OCT ) devices : the time domain ( TD ) Stratus OCT and two spectral domain ( SD ) OCTs , Spectralis and Cirrus SD-OCT , in eyes with macular edema secondary to diabetic retinopathy ( DR ) and retinal vein occlusion ( VO ) . Methods . In a prospect i ve observational study at a university-based retina practice , retinal thickness tomography was performed simultaneously for fifty-eight patients ( 91 eyes ) with DR and VO employing a time domain and two spectral domain 
    Output:
    
Ocular neurodegenerative changes are more evident when diabetic retinopathy or polyneuropathy is present .
OCT and CCM are potentially useful , in addition to conventional clinical methods , to assess diabetic neurodegenerative changes .